CONFIRMATION OF DAMAGING EFFECT OF MSH2 c.2634+1G > C MUTATION ON SPLICING, ITS CLASSIFICATION AND IMPLICATIONS FOR COUNSELING
Lynch Syndrome (LS) is a hereditary cancer syndrome which is characterized by the most frequent cancer localizations in colorectum and endometrium. Aside from familial aggregation of cancer, the striking hallmarks of this hereditary cancer syndrome are early diagnosis of these two types of carcinomas ( (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - August 14, 2019 Category: Genetics & Stem Cells Authors: Rakobradovi ć Jelena, Krivokuća Ana, Jovandić Stevo, Kesić Vesna, Branković-Magić Mirjana Tags: Original Article Source Type: research

Cytogenomic Characterization of Double Minute Heterogeneity in Therapy Related Acute Myeloid Leukemia
Somatic perturbations such as translocation, mutation, deletion, gene amplification and epigenetic modification in proto-oncogenes and/or tumor suppressor genes may result in unscheduled expression of proto-oncogenes, or altered function of tumor suppressor genes, or cause gene overexpression in tumors. Gene amplification is a unique form of genomic instability in cancer genome and is often considered a biomarker for aggressive disease that is resistant to therapy. While low level amplification is represented by copy number gains (trisomy or tetrasomy), high level amplification may manifest morphologically as a homogeneous...
Source: Cancer Genetics and Cytogenetics - August 6, 2019 Category: Genetics & Stem Cells Authors: Prasad Koduru, Weina Chen, Barbara Haley, Kevin Ho, Dwight Oliver, Kathleen Wilson Tags: Case Report Source Type: research

Masked hypodiploidy: hypodiploid acute lymphoblastic leukemia (ALL) mimicking hyperdiploid ALL in children: A report from the Children's Oncology Group
Hyperdiploidy with greater than 50 chromosomes is usually associated with favorable prognosis in pediatric acute lymphoblastic leukemia (ALL), whereas hypodiploidy with ≤43 chromosomes is associated with extremely poor prognosis. Sometimes, hypodiploidy is “masked” and patients do not have a karyotypically visible clone with ≤43 chromosomes. Instead, their abnormal karyotypes contain 50–78 or more chromosomes from doubling of previously hypodiploid cells. When the hypodiploid and doubled hyperdiploid clones are both present, patients can be identified by traditional test methods [karyotype, DNA Inde...
Source: Cancer Genetics and Cytogenetics - July 30, 2019 Category: Genetics & Stem Cells Authors: Andrew J Carroll, Mary Shago, Fady M Mikhail, Susana C Raimondi, Betsy A Hirsch, Mignon L Loh, Elizabeth A Raetz, Michael J Borowitz, Brent L Wood, Kelly W Maloney, Leonard A Mattano, Eric C Larsen, Julie Gastier-Foster, Eileen Stonerock, Denise Ell, Sami Source Type: research

Telomere length measurement in tumor and non ‐tumor cells as a valuable prognostic for tumor progression
Telomeres are composed by a repetitive DNA sequence (in humans: TTAGGG repeated up to 1500 times) which constitutes the end of each chromosome arm and associates with various proteins constituting the Shelterin complex [1]. This complex allows telomere folding to form the D-loop and the T-loop, protecting chromosomes from fusion or degradation and hence preventing chromosomal instability [2]. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - July 26, 2019 Category: Genetics & Stem Cells Authors: Fatma Mehrez, Karim Bougatef, Elisa Delle Monache, Ivan Arisi, Luca Proietti-De-Santis, Giorgio Prantera, Lilia Zouiten, Manuela Caputo, Amel Ben Ammar Elgaaied, Silvia Bongiorni Tags: Original Article Source Type: research

Clinical implications of clonal chromosomal abnormalities in Philadelphia negative cells in CML patients after treated with tyrosine kinase inhibitors
Chronic myelogenous leukemia (CML) is a clonal hematologic disorder characterized by the presence of a fusion oncogene, BCR-ABL, which leads to uncontrolled proliferation of myeloid cells. The fusion gene is the results of reciprocal translocation (9;22) (q34; q11) known as Philadelphia (Ph) chromosome[1]. The successful use of tyrosine kinase inhibitors (TKIs) targeting the BCR-ABL oncoprotein has significantly improved the prognosis of this disease, so that the survival of CML patients is nearly identical to that of the general population[2,3]. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - July 24, 2019 Category: Genetics & Stem Cells Authors: Hongyu Ni, Xinlai Sun, Yin Xu, Derek Lyle, Paris Petersen, Xianfeng Zhao, Hong Drum, Bei You, Dongfang Liu, Chen Liu, Jie-Gen Jiang Source Type: research

RUNX1 Deletion/Amplification in Therapy-Related Acute Myeloid Leukemia: A Case Report and Review of the Literature
We describe here a case of AML with apparent amplification of RUNX1 by cytogenetics and FISH. A 39-year-old female in remission from stage IIIa breast cancer was diagnosed with therapy-related AML (t-AML). The patient's bone marrow was hypocellular for her age (30-40%) with 25% blasts. Cytogenetic analyses revealed a complex karyotype, characterized by rearrangements in chromosomes 1, 5, 17, 20, an additional unidentified marker chromosome, and apparent amplification of chromosome 21. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - July 24, 2019 Category: Genetics & Stem Cells Authors: David Nguyen, Yuwen Li, Hana Safah, Theresa C. Brown Tags: Case Report Source Type: research

Detection of a novel CBFB-MYH11 fusion transcript in acute myeloid leukemia M1 with inv(16)(p13q22)
Acute myeloid leukemia (AML) with an inv(16)(p13q22) or t(16;16)(p13;q22) chromosomal abnormality represents one of the most common subtypes of de novo cases. These chromosomal rearrangements result in multiple CBFB-MYH11 fusion transcripts, with type-A being the most frequent. We here describe a unique case of de novo AML-M1, with inv(16)(p13q22), leading to an unusual CBFB-MYH11 fusion transcript, and der(7)t(7;11)(q31;q21). The fusion transcript involves a CBFB exon 5 with a breakpoint at nucleotide 754, an insertion of a 13-bp sequence of CBFB intron 5 at the fusion point, and the MYH11 exon 27 with a breakpoint at nuc...
Source: Cancer Genetics and Cytogenetics - July 24, 2019 Category: Genetics & Stem Cells Authors: Keiji Kurata, Katsuya Yamamoto, Yoko Okazaki, Yoriko Noguchi, Keiji Matsui, Hisayuki Matsumoto, Yumiko Inui, Kimikazu Yakushijin, Mitsuhiro Ito, Yuji Nakamachi, Hiroshi Matsuoka, Jun Saegusa, Hironobu Minami Tags: Case Report Source Type: research

Chronic myelomonocytic leukemia with ETV6-ABL1 rearrangement and SMC1A mutation
We report a patient who had a clinical and morphological presentation consistent with CMML. The genetic work-up showed an ETV6-ABL1 fusion consequent to a 9;12 translocation, and a missense mutation in SMC1A (c.1757G>A, p.Arg586Gln). (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - July 13, 2019 Category: Genetics & Stem Cells Authors: Melissa H. Cessna, Prabakaran Paulraj, Benjamin Hilton, Kianoush Sadre-Bazzaz, Philippe Szankasi, Alice Cluff, Jay L. Patel, Daanish Hoda, Reha M. Toydemir Tags: Case Report Source Type: research

Variants in COL6A3 gene influence susceptibility to esophageal cancer in the Chinese population
Esophageal cancer (EC) is considered a most common gastrointestinal malignant cancer in our world (1). It has a highly morbidity and mortality, more than 450,000 new cases of EC were diagnosed, and about 400,000 patients were died in each year (2). According to histological type, EC was classified two different forms, esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) (3). Several reports revealed that ESCC is the main histological subtype of EC in developing countries (4). (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - July 13, 2019 Category: Genetics & Stem Cells Authors: Yang Li, Yao Sun, Qinshuai Yang, Jiamin Wu, Zichao Xiong, Shanqu Li, Tianbo Jin Tags: Original Article Source Type: research

ANKRD26-RET - A novel gene fusion involving RET in papillary thyroid carcinoma
Since the 1990s, rearrangements of the RET gene were discovered as molecular alterations responsible for tumorigenesis in different cancer types. In approximately one third of papillary thyroid carcinoma cases, RET rearrangements are detectable, with a variation depending on geographical background and the applied method of assessment [1 –4]. In 1-2% of non-small cell lung cancer, RET rearrangements are detected [5]. Moreover, RET rearrangements were reported in breast cancer, colorectal cancer and other tumor entities (Table 1). (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - July 5, 2019 Category: Genetics & Stem Cells Authors: Julia Isabelle Staubitz, Thomas Johannes Musholt, Arno Schad, Erik Springer, Hauke Lang, Krishnaraj Rajalingam, Wilfried Roth, Nils Hartmann Tags: Original article Source Type: research

Homogeneously Staining Region (hsr) on Chromosome 11 Is Highly Specific for KMT2A Amplification in Acute Myeloid Leukemia (AML) and Myelodysplastic syndrome (MDS)
Acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) are common myeloid neoplasms that affect mainly older patients [1]. Both AML and MDS are heterogeneous groups of diseases that are subclassified into multiple types based on clinical, pathologic and genetic abnormalities; many of them show substantial differences in prognosis and ultimate outcome and, in some instances, require different therapeutic interventions [2,3]. Overexpression of certain proto-oncogenes plays an indispensable role in tumorgenesis of AML and MDS and results in enhanced proliferation and impaired differentiation of leukemic stem cells [4...
Source: Cancer Genetics and Cytogenetics - July 5, 2019 Category: Genetics & Stem Cells Authors: Ali Sakhdari, Zhenya Tang, Chi Young Ok, Carlos E. Bueso-Ramos, L. Jeffrey Medeiros, Yang O. Huh Tags: Original Article Source Type: research

Cytogenetic profile of a representative cohort of young adults with de novo Acute My éloblastic Leukaemia in Morocco
This is the largest study done in Morocco, Africa and Middle East. Epidemiological studies involving different ethnic populations and geographic regions of the world should help unfold the true nature of environmental and genetic interplay in the development of AML. Our cytogenetic profile reveals some particularities when compared to other populations; it doesn't seem to be similar neither to eastern or western countries. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - June 15, 2019 Category: Genetics & Stem Cells Authors: Nisrine Khoubila, Mounia Bendari, Nezha Hda, Mouna Lamchahab, Meryem Qachouh, Mohamed Rachid, Asmaa Quessar Tags: Original Article Source Type: research

Single-cell cloning of human T-cell lines reveals clonal variation in cell death responses to chemotherapeutics
CRISPR-Cas9 is a highly versatile approach for genetic manipulation of primary cells and transformed cell lines [1,2]. However, the gene editing efficiency in some cell types, including human T-cell lines, is highly variable [3,4]. The human Jurkat T-cell line has been reported to reach editing efficiencies of up to 75% for single edits but lower than 1% for double edits targeting a large kbp region [5,6]. In the latter case, clonal isolation of cell lines is often used to enable the study of gene function [7,8]. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - June 12, 2019 Category: Genetics & Stem Cells Authors: Kathleen Hanlon, Alex Thompson, Lorena Pantano, John N. Hutchinson, Arshed Al-Obeidi, Shu Wang, Meghan Bliss-Moreau, Jennifer Helble, Gabriela Alexe, Kimberly Stegmaier, Daniel E. Bauer, Ben A. Croker Tags: Short Communication Source Type: research

A Unique Case of Complex Variant Translocation of t(6;9;22)(p22;q34;q11.2), der(19) in a Newly Diagnosed Patient with Chronic Myeloid Leukemia
Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder characterized by the dysregulated production and uncontrolled proliferation of myeloid neoplastic cells. CML is associated with the fusion of BCR (on chromosome 22) and ABL1 (on chromosome 9) resulting in the BCR-ABL1 fusion gene. The translocation of chromosomes (9;22)(q34;p15) is present in almost 90-95% of patients with CML and only 5-8% CML patients have established variant complex translocation due to the participation of one or more chromosomes other than 9 and 22 chromosome. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - June 12, 2019 Category: Genetics & Stem Cells Authors: Rafiye Çiftçiler, Emine Arzu Saglam, Ayten Inanc, Osman Ozcebe, Ibrahim Celalettin Haznedaroglu Tags: Case Report Source Type: research

Inherited cancer syndromes in 220 Italian ovarian cancer patients
Ovarian cancer (OC) is the third most common gynaecological malignancy in Europe. Owing to its unfavorable anatomy and lack of effective screening strategies, it is often diagnosed as advanced stage disease and it has the highest mortality rate of all gynaecological malignancies [1]. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - June 12, 2019 Category: Genetics & Stem Cells Authors: I. Carnevali, C. Riva, A.M. Chiaravalli, N. Sahnane, E. Di Lauro, A. Viel, F. Rovera, G. Formenti, F. Ghezzi, F. Sessa, M.G. Tibiletti Tags: Original Article Source Type: research

Concurrent chromothripsis events in a case of TP53 depleted Acute Myeloid Leukemia with myelodysplasia-related changes
Acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) mostly affects elderly adults. It is a heterogeneous disorder with poor prognosis, defined by morphological, genetic, and clinical features. Genetic abnormalities, such as -5/del(5q), -7/del(7q), and/or complex karyotypes are often detected and associated with AML-MRC [1]. The presence of ≥20% blasts in peripheral blood (PB) or bone marrow and multi-lineage dysplasia affecting ≥50% cells in two or more myeloid lineages is often thought to be straightforward criteria for AML-MRC diagnosis. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - June 12, 2019 Category: Genetics & Stem Cells Authors: D. Tolomeo, A. L'Abbate, A. Lonoce, P. D'Addabbo, M.F. Miccoli, C. Lo Cunsolo, P. Iuzzolino, O. Palumbo, M. Carella, V. Racanelli, T. Mazza, E. Ottaviani, G. Martinelli, G. Macchia, C.T. Storlazzi Tags: Short Communication Source Type: research

Prevalence and founder effect of the BRCA1 p.(Val1833Met) variant in the Greek population, with further evidence for pathogenicity and risk modification
The diverse mutational spectrum in the Greek population among hereditary breast and/or ovarian cancer patients was recently described in detail, concerning predominantly BRCA1, followed by BRCA2 pathogenic variants. Interestingly, about 75% of all BRCA1 pathogenic variants are located at the 3 ΄ end of the gene, attributed mainly to strong founder effects, while BRCA2 pathogenic variants are scattered along the gene sequence. Although the Greek population is characterized by genetic heterogeneity, Greek founder pathogenic variants account for approximately 68.5% of all BRCA1 pathogenic v ariants detected, suggesting a rea...
Source: Cancer Genetics and Cytogenetics - June 12, 2019 Category: Genetics & Stem Cells Authors: Myrto Papamentzelopoulou, Paraskevi Apostolou, Florentia Fostira, Constantine Dimitrakakis, Dimitris Loutradis, George Fountzilas, Drakoulis Yannoukakos, Irene Konstantopoulou Source Type: research

Characterization of a rarely reported STAT5B/RARA gene fusion in a young adult with newly diagnosed acute promyelocytic leukemia with resistance to ATRA therapy
A 27-year-old male without a past medical history presented to the emergency room with a week of migratory muscle aches and sweats along with a 2-month history of progressive fatigue. A complete blood count revealed anemia (hemoglobin, 5 g/dL; reference, 13.2-16.6 g/dL), thrombocytopenia (platelet count, 24  × 103/μL; reference, 135-317 × 103/μL), and leukocytosis (white blood cell (WBC) count, 52 × 103/μL; reference, 3.4-9.6 103/μL). A subsequent bone marrow evaluation demonstrated marrow replacement (nearly 100%) by predominantly intermediate to large mononuclear and rare bilobed...
Source: Cancer Genetics and Cytogenetics - June 12, 2019 Category: Genetics & Stem Cells Authors: Jess F. Peterson, Rui R. He, Hassan Nayer, Raymund S. Cuevo, James B. Smadbeck, George Vasmatzis, Patricia T. Greipp, Rhett P. Ketterling, Nicole L. Hoppman, Linda B. Baughn Tags: Case Report Source Type: research

Expression deregulation of DNA repair pathway genes in gastric cancer
Oxidative DNA damage and DNA repair mediate the development of several human pathologies, including gastric cancer. The major pathway for oxidative DNA damage repair is base excision repair (BER) pathway [1]. Base excision repair (BER) is the primary guardian pathway against damage that results from cellular metabolism, including reactive oxygen species, methylation, deamination and hydroxylation. Therefore, base excision repair is a universal event in cells and is relevant for preventing mutagenesis [2]. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - June 11, 2019 Category: Genetics & Stem Cells Authors: Shahzad Yousaf, Asad Ullah Khan, Zertashia Akram, Mahmood Akhtar Kayani, Iram Nadeem, Bilquis Begum, Ishrat Mahjabeen Source Type: research

Non-invasive genotyping of metastatic colorectal cancer using circulating cell free DNA
Both men and women have a lifetime risk of colorectal cancer (CRC) of about 1 in 20 [1,2]. It was estimated in 2017 that more than 125,000 people would be diagnosed with CRC, and more than 50,000 would die of the disease. Nearly 1 in 5 CRC patients have late-stage disease at diagnosis [3], which greatly diminishes treatment opportunities and contributes to a 5-year survival rate as low as 12% [4]. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - June 11, 2019 Category: Genetics & Stem Cells Authors: Xuemei Shi, Dzifa Y. Duose, Meenakshi Mehrotra, Michael A. Harmon, Peter Hu, Ignacio I. Wistuba, Scott Kopetz, Rajyalakshmi Luthra Tags: Original Article Source Type: research

PD-L1 gene copy number and promoter polymorphisms regulate PD-L1 expression in tumor cells of non-small cell lung cancer patients
Immunotherapy with immune-checkpoint inhibitors is a promising treatment method for locally advanced or advanced non-small cell lung cancer (NSCLC) patients. Monoclonal antibodies against programmed death 1 (PD-1) and against its ligand (PD-L1) are used in several indications. Nivolumab (anty-PD-1 antibody) and atezolizumab (anti-PD-L1 antibody) were approved in second line therapy in a wide group of NSCLC patients [1, 2]. While pembrolizumab (anti-PD-1 antibody), in monotherapy, could be used in first or second line treatment of NSCLC patients with PD-L1 expression on tumor cells. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - June 7, 2019 Category: Genetics & Stem Cells Authors: Pawe ł Krawczyk, Anna Grenda, Kamila Wojas-Krawczyk, Marcin Nicoś, Tomasz Kucharczyk, Bożena Jarosz, Katarzyna Reszka, Juliusz Pankowski, Kinga Krukowska, Aleksandra Bożyk, Justyna Szumiło, Marek Sawicki, Tomasz Trojanowski, Janusz Milanowski Tags: Original Article Source Type: research

p53 major hotspot variants are associated with poorer prognostic features in hereditary cancer patients
TP53 pathogenic germline variation is associated with the multi-cancer predisposition Li-Fraumeni syndrome (LFS). Next-generation sequencing and multigene panel testing are highlighting variability in the clinical presentation of patients with TP53 positive results. We aimed to investigate if the p53 variants considered as major hotspots at both germline and somatic levels (p.Arg175His, p.Gly245Asp, p.Gly245Ser, p.Arg248Gln, p.Arg248Trp, p.Arg273Cys, p.Arg273His, and p.Arg282Trp) were associated with poorer prognostic features compared to other pathogenic missense variants in the DNA-binding domain. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - June 6, 2019 Category: Genetics & Stem Cells Authors: Cristina Fortuno, Tina Pesaran, Jill Dolinsky, Amal Yussuf, Kelly McGoldrick, Pik Fang Kho, Paul A. James, Amanda B. Spurdle Tags: Original Article Source Type: research

Association of Transcriptional Levels of Folate-Mediated One-Carbon Metabolism-Related Genes in Cancer Cell Lines with Drug Treatment Response
Folate-mediated one-carbon metabolism (OCM), which involves folate and methionine cycles, regulates cellular nutrient status and redistribution of one-carbon units into reactions and processes that are vital for cellular functions (1,2). One-carbon units generated from folic acid and amino acids are used for cellular biosynthesis, regulation of redox status, nucleic acid and protein methylation, and genome maintenance, which are necessary for cell growth and survival (1,3). The folate cycle involves multiple biosynthetic reactions in the cytoplasm, mitochondria, and the nucleus (1,4,5). (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - June 5, 2019 Category: Genetics & Stem Cells Authors: Dong-Joon Min, Suleyman Vural, Julia Krushkal Tags: Original Article Source Type: research

Down-regulation of STIP1 regulate apoptosis and invasion of glioma cells via TRAP1/AKT signaling pathway
Glioma is the most common primary malignant tumor in the brain; it has the characteristics of “three highs and one low” and is characterized by and its high incidence, high recurrence rate, high mortality rate, and low cure rate (1,2). Glioblastoma is the most common type of glioma. The median overall survival time for glioblastoma is approximately 14.6 months, and with standard treatmen t and diagnosis, the 5-year survival rate is less than 9.8% (3,4). It is therefore imperative to study the molecular mechanisms of glioma and identify new treatment strategies. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - June 3, 2019 Category: Genetics & Stem Cells Authors: Hongwei Yin, ZhiTong Deng, Xuetao Li, YanYan Li, Wenhao Yin, Guozhen Zhao, Dongyang Jiang, Chunming Sun, Youxin Zhou Tags: Original Article Source Type: research

Editorial Board
(Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - June 1, 2019 Category: Genetics & Stem Cells Source Type: research

Classic bladder exstrophy and adenocarcinoma of the bladder: methylome analysis provide no evidence for underlying disease-mechanisms of this association
The bladder exstrophy-epispadias complex represents the severe end of human congenital anomalies of the kidney and urinary tract (CAKUT) that also involves defect in abdominal wall, pelvis, genitalia, occasionally the spine and anus [1, 2]. The severity-spectrum of the BEEC comprises the mild form (epispadias/E), intermediate form (classic bladder exstrophy/CBE), and the severe form (exstrophy of the cloaca/CE). Long-term complications of CBE are malignancies of the bladder with 95% of these being adenocarcinomas [3]. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - May 31, 2019 Category: Genetics & Stem Cells Authors: Amit Sharma, Holger Fr öhlich, Rong Zhang, Anne-Karoline Ebert, Wolfgang Rösch, Henning Reis, Glen Kristiansen, Jörg Ellinger, Heiko Reutter Tags: Short Communication Source Type: research

A novel CHEK2 variant identified by next generation sequencing in an Indian family with hereditary breast cancer syndrome
We report a BRCA negative family with multiple affected women having breast cancer, with a novel, missense, likely pathogenic variant in the CHEK2 gene (c.1376T>G; p.Ile459Ser) that segregated with subjects with breast cancer. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - May 31, 2019 Category: Genetics & Stem Cells Authors: Dr. Pratibha Sharma Bhai, Dr. Renu Saxena, Samarth Kulshrestha, Dr. Ishwar Chander Verma Tags: Case Report Source Type: research

Acute lymphoblastic leukemia in a nine-year-old girl with isodicentric chromosome 15 syndrome
Isodicentric chromosome 15, also called idic(15), is a rare chromosomal abnormality resulting from inverted duplication of proximal 15q. It is associated with specific clinical findings such as early central hypotonia, developmental delay, cognitive dysfunction, autism spectrum disorders, and seizure. Herein we describe a case of a girl with idic(15) syndrome who developed acute lymphoblastic leukemia (ALL) at the age of 9 years. Our case suggests a possible correlation between idic(15) and ALL, and possible functional links between these two conditions. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - May 18, 2019 Category: Genetics & Stem Cells Authors: Roberto Antonucci, Nadia Vacca, Elisa Ghisu, Gloria Acquaviva, Carlo Cosmi, Anna Maria Marinaro, Cristian Locci, Claudio Fozza Tags: Letter to the Editor Source Type: research

FANCM, RAD1, CHEK1 and TP53I3 Act as BRCA-like Tumor Suppressors and are Mutated in Hereditary Ovarian Cancer
Despite the large heritable component to OVCA, the majority of underlying genetic risk remains unexplained [1]. OVCA is rare, displays variable penetrance, and has a high degree of underlying genetic heterogeneity. The clinical implications of a novel risk locus, is therefore difficult to accurately establish through case control associative studies [2, 3]. Additionally, implicating a variant based on segregation is not ideal due to incomplete penetrance and lack of informative family members. Whole exome/genome sequencing (WES/WGS) of affected individuals with compelling family histories is a promising approach for the id...
Source: Cancer Genetics and Cytogenetics - April 29, 2019 Category: Genetics & Stem Cells Authors: Jaime L. Lopes, Sophia Chaudhry, Guilherme S. Lopes, Nancy K. Levin, Michael A. Tainsky Tags: Original Article Source Type: research

Outcomes of Disease-Specific Next-Generation Sequencing Gene Panel Testing in Adolescents and Young Adults with Colorectal Cancer
Colorectal cancer (CRC) has typically been considered a disease affecting individuals older than age 50. However, recent data has demonstrated a trend of increasing numbers of patients under age 50 diagnosed with CRC. In fact, the rate of CRC in individuals between ages 20-34 is anticipated to increase 90.0-124.2% by 2030 if current rates continue [1]. Although the cause for this increase is not fully understood, potential risk factors include obesity, physical inactivity, increased red meat intake, and decreased vegetable consumption. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - April 26, 2019 Category: Genetics & Stem Cells Authors: Maureen E. Mork, Andrea Rodriguez, Sarah A. Bannon, Patrick M. Lynch, Miguel A. Rodriguez-Bigas, Selvi Thirumurthi, Y. Nancy You, Eduardo Vilar Tags: Original Article Source Type: research

Somatic Mutation Panels: Time to clear their names
A 65 year old woman with a history of an ER+ PR+ HER2+ invasive ductal carcinoma of the right breast diagnosed at age 34, status-post lumpectomy/radiation/and chemotherapy presented to the Hematology Clinic with newly diagnosed chronic lymphocytic leukemia (CLL). Panel-based next generation sequencing (NGS) was conducted on the peripheral blood and revealed a TP53 (c.743G>A, p.R248Q) mutation with a variant allele fraction (VAF) of 45%. Due to anemia and constitutional symptoms, she began treatment with ibrutinib. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - April 26, 2019 Category: Genetics & Stem Cells Authors: Amy M. Trottier, Marcela Cavalcante de Andrade Silva, Zejuan Li, Lucy A. Godley Tags: Review Article Source Type: research

Retrotransposon Elements among Initial Sites of Hepatitis B Virus Integration into Human Genome in the HepG2-NTCP Cell Infection Model
Hepatitis B virus (HBV) is one of the most common and deceitful human pathogens that causes liver injury ranging from an asymptomatic disease through acute and chronic hepatitis type B, to liver cirrhosis and primary hepatocellular carcinoma (HCC) [1]. HBV is recognized as the most potent viral oncogene responsible for thousands of liver cancer-related deaths annually [2]. Its oncogenic potency has been primarily aligned with integration of viral DNA into hepatocyte genome capable of compromising cell genome stability and modifying expression of individual genes [3]. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - April 24, 2019 Category: Genetics & Stem Cells Authors: Ranjit Chauhan, Yoshimi Shimizu, Koichi Watashi, Takaji Wakita, Masayoshi Fukasawa, Tomasz I Michalak Tags: Original Article Source Type: research

Uptake of genetic testing for germline BRCA1/2 pathogenic variants in a predominantly Hispanic population
Genetic counseling is under-utilized in women who meet family history criteria for BRCA1 and BRCA2 (BRCA1/2) testing, particularly among racial/ethnic minorities. We evaluated the uptake of BRCA1/2 genetic testing among women presenting for screening mammography in a predominantly Hispanic, low-income population of Washington Heights in New York City. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - April 24, 2019 Category: Genetics & Stem Cells Authors: Julia E. McGuinness, Meghna S. Trivedi, Thomas Silverman, Awilda Marte, Jennie Mata, Rita Kukafka, Katherine D. Crew Tags: Short Communication Source Type: research

Circulating cell-free DNA integrity as a diagnostic and prognostic marker for breast and prostate cancers
The incidence of cancer and its related mortality is on the rise and has become a major public health concern. Currently, it is the second leading cause of death globally and was responsible for about 8.82 million deaths in, 2015 [1]. The international Agency for Research on Cancers of the WHO in 2012 projected that by the year 2030, there would be approximately 21.7 million new cancer cases and 13 million cancer deaths globally due to population growth and increased life expectancy [2]. Cancer incidence and mortality over the years have also seen a steady rise on the African continent with breast and prostate cancers amon...
Source: Cancer Genetics and Cytogenetics - April 23, 2019 Category: Genetics & Stem Cells Authors: Benjamin Arko-Boham, Nii Ayite Aryee, Richard Michael Blay, Ewurama Dedea Ampadu Owusu, Emmanuel Ayitey Tagoe, Eshirow-Sam Doris Shackie, Ama Boatemaa Debrah, Armah Nii Adu-Aryee Tags: Original Article Source Type: research

Prevalence and characteristics of likely-somatic variants in cancer susceptibility genes among individuals who had hereditary pan-cancer panel testing
Mosaicism is defined as the presence of two or more cell populations with unique genotypes in one individual. Low-level mosaicism is seen frequently in normal tissues, and particularly in those with higher turnover rates.[1] One such tissue is bone marrow, which produces the peripheral white blood cells that comprise a common source of genomic DNA used in next-generation sequencing (NGS) hereditary pan-cancer panel testing. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - April 13, 2019 Category: Genetics & Stem Cells Authors: Thomas P. Slavin, Bradford Coffee, Ryan Bernhisel, Jennifer Logan, Hannah C. Cox, Guido Marcucci, Jeffrey Weitzel, Susan L. Neuhausen, Debora Mancini-DiNardo Tags: Original Article Source Type: research

Aberrant methylation status of SPG20 promoter in Hepatocellular Carcinoma: a potential tumor metastasis biomarker
Hepatocellular carcinoma (HCC) is the sixth highest malignant tumor in the world. Because of its complicated pathogenesis, high recurrence, metastasis rate and tumor heterogeneity, HCC has become the third most frequent cause of cancer-related death (1). However, the 5-year survival of HCC patients can achieve higher than 50% when diagnosis at early stages (2).Therefore, a better understand of the pathogenesis for HCC is critical to improve the prognosis of patients with HCC through early diagnosis and treatment. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - April 12, 2019 Category: Genetics & Stem Cells Authors: Lifeng He, Xiaoxiao Fan, Yirun Li, Bin Cui, Zhaoqi Shi, Daizhan Zhou, Hui Lin Source Type: research

A comparison of survival analysis methods for cancer gene expression RNA-Sequencing data
All large-scale cancer profiling studies consistently share a common feature that support the notion that cancer is a complex, heterogeneous genetic disease. Collections of genome-wide transcriptional profiling datasets captured using technologies like microarrays and RNA-sequencing (RNA-seq) have improved our insight into the nature of this heterogeneity for many different tumor types. Through efforts such as the Cancer Genome Atlas (TCGA) (1), the Expression Oncology Project (expO) (2), and projects stemming from the International Cancer Genome Consortium (ICGC) (3), gene expression datasets are publicly accessible with ...
Source: Cancer Genetics and Cytogenetics - April 12, 2019 Category: Genetics & Stem Cells Authors: Pichai Raman, Samuel Zimmerman, Komal S. Rathi, Laurence de Torrent é, Mahdi Sarmady, Chao Wu, Jeremy Leipzig, Deanne M. Taylor, Aydin Tozeren, Jessica C. Mar Source Type: research

PIP4K2A and PIP4K2C transcript levels are associated with cytogenetic risk and survival outcomes in acute myeloid leukemia
The phosphoinositide signaling pathway orchestrates primordial molecular and cellular functions in both healthy and pathologic conditions, including cell proliferation, survival, apoptosis, and cell motility (1,2). Phosphatidylinositol-5-phosphate 4-kinase type 2 (PIP4K2) is a lipid kinase family that contains three members, PIP4K2A, PIP4K2B and PIP4K2C (also known as type II PIP4K α, PIP4Kβ and PIP4Kγ or PIP5K2A, PIP5K2B and PIP5K2C, respectively). These proteins phosphorylate the phosphatidylinositol (PtdIns)5P at the position four of the inositol ring producing PtdIns4,5P2, which is important for phosph...
Source: Cancer Genetics and Cytogenetics - April 11, 2019 Category: Genetics & Stem Cells Authors: Keli Lima, Juan Luiz Coelho-Silva, Gabriela Sarti Kinker, Diego Antonio Pereira-Martins, Fabiola Traina, Pedro Augusto Carlos Magno Fernandes, Regina Pekelmann Markus, Antonio Roberto Lucena-Araujo, Jo ão Agostinho Machado-Neto Tags: Original Article Source Type: research

Prognostic significance of CDC25C in lung adenocarcinoma: an analysis of TCGA data
Lung adenocarcinoma (LUAD) is the most common and aggressive type of non-small cell lung cancer (NSCLC), accounting for around 40% of all lung cancers, and is an important cause of respiratory cancer deaths [1]. Lung and bronchus cancers represent 14% and 12% of all cancers in men and women, respectively, making it the second most frequent cancer in both sexes [2, 3]. The 5-year relative survival rate for lung cancer was 18% in 2007 –2013 [2]. LUAD is typically diagnosed at an advanced stage, after metastasis [4]. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - April 9, 2019 Category: Genetics & Stem Cells Authors: Zengfei Xia, Wen Ou-yang, Ting Hu, Ketao Du Tags: Original Article Source Type: research

1. Building a pretreatment risk-stratification model for follicular lymphoma with genomic alterations and clinical parameters
Follicular lymphoma (FL) is a heterogeneous disease with variable outcome. Current pretreatment risk assessment methods focus on clinical parameters, such as the FL international prognostic index (FLIPI), FLIPI-2, PRIMA-PI, and PET. Although robust, these clinical scoring systems are limited in clinical utility and have not yet informed a precision approach to treatment. Integration of tumor gene mutations has been shown to improve FL prognosis with a clinicogenetic risk model, the m7-FLIPI score, which included the mutation status of seven genes (EZH2, ARID1A, MEF2B, EP300, FOXO1, CREBBP, and CARD11), the FLIPI, and ECOG ...
Source: Cancer Genetics and Cytogenetics - April 1, 2019 Category: Genetics & Stem Cells Authors: Xiaoyu Qu, Hongli Li, Verena Passerini, Oliver Weigert, Michael LeBlanc, Jonathan W. Friedberg, Min Fang Source Type: research

2. Non-random distribution of copy number variants in hematologic neoplasms with chromothripsis
The theory of cancerogenesis as a progressive multi-step accumulation of somatic genetic alterations has changed with the discovery of chromothripsis, a single catastrophic event of chromosome shattering, which results in a big number of CNVs. Chromothripsis has been reported in a wide range of cancers in association with an adverse prognosis, gaining reputation of a high-risk marker. We performed SNP-array analysis (Affymetrix ®) on series of newly diagnosed or relapsed neoplasms of myeloid [40 cases of AML and 3 cases of MDS] and lymphoid [13 cases of Mantle Cell Lymphoma (MCL)] origin and selected cases with chromot...
Source: Cancer Genetics and Cytogenetics - April 1, 2019 Category: Genetics & Stem Cells Authors: Madina Sukhanova, Juehua Gao, Yi-Hua Chen, Girish Venkataraman, Yanming Zhang, Xinyan Lu, Lawrence Jennings, Amir Behdad Source Type: research

3. Integrated whole-genome sequencing and bioinformatics analysis for copy number profiling identifies a recurrent alteration associated with poor survival in Stage III colorectal cancer
This study aims to develop an integrated whole-genome sequencing (WGS) and bioinformatics approach for accurate and cost-effective profiling of CNA biomarkers in clinics. We utilized a low-depth WGS approach to profile CNAs for matched formalin-fixed paraffin-embedded tumor-normal samples. We developed a bioinformatic pipeline based on systematic evaluation of genome segmentation, CNA detection and statistical tools. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - April 1, 2019 Category: Genetics & Stem Cells Authors: Li Charlie Xia, Hojoon Lee, Sue Grimes, Matt Kubit, Paul Van Hummelen, Lincoln Nadauld, Hanlee Ji Source Type: research

4. Molecular characterizations of adult diffuse gliomas by the Oncoscan CNV Plus assay and next-generation sequencing (NGS)
Diffuse gliomas, including astrocytomas, oligodendrogliomas and glioblastomas (GBMs), are incurable. Recent molecular and cytogenomic profiling have enabled tumor classification for clinical management. To assess the genomic aberrations, we applied FISH, next generation sequencing (NGS) and the Oncoscan assay in 48 adult diffuse gliomas, including 9 oligodendrogliomas, 8 grade II/III astrocytomas, and 31 GBMs. Oligodendrogliomas were characterized by 1p/19q co-deletions and the IDH1 (R132H, n  = 8) or IDH2 (R172K, n = 1) mutations, with concurrent mutations in TERT, (62.5%), CIC (55.6%), and FUBP1 (22.2%). (Source:...
Source: Cancer Genetics and Cytogenetics - April 1, 2019 Category: Genetics & Stem Cells Authors: Xinyan Lu, Madina Sukhanova, Juehua Gao, Craig Horbinski, Larry Jennings, Qinwei Mao, Eileen Bigio, Daniel Brat, Christina Appin Source Type: research

5. Detecting mutations in cerebrospinal fluid: liquid biopsy for diagnosis of central nervous system metastases
There is a critical need for better methodologies to diagnose and monitor patients with central nervous system (CNS) tumors. The use of circulating tumor DNA (ctDNA) is a promising tool for evaluating patients with primary or metastatic CNS tumors. Cerebrospinal fluid (CSF) is more suitable to detect ctDNA from CNS cancers than plasma, due to the effects of blood-brain barrier. The current techniques for diagnosing CNS tumors include imaging, CSF-cytology and biopsies. Imaging and CSF-cytology have poor specificity and sensitivity, respectively, and biopsies are invasive. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - April 1, 2019 Category: Genetics & Stem Cells Authors: Mauli Shah, Soheil Zorofchian, Chieh Lan, Dzifa Duose, Peter Hu, Yoshua Esquenazi, Rajyalakshmi Luthra, Leomar Y. Ballester Source Type: research

6. Expansion of the validation of Illumina MethylationEPIC BeadChip for medulloblastoma (MB) subgrouping and copy number analysis across institutions and results from the initial 47 clinical cases
Background: MB is a common pediatric brain tumor traditionally risk-stratified using age, histology, metastasis and extent of resection. Gene expression studies show four major subgroups: WNT, SHH, Group 3 and Group 4. Profiling using the Illumina Methylation450 BeadChip helps subgroup these tumors. Additional studies show these subgroups have characteristic copy number changes (CNC). We expanded our initial validation cohort for MB subgrouping and copy number analyses (CNA). (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - April 1, 2019 Category: Genetics & Stem Cells Authors: Teresa Smolarek, Brenna Hott, Ralph Salloum, Christine Fuller, Vijay Ramaswamy, Michael Taylor, Maryam Fouladi, Lisa Dyer, Rachid Drissi Source Type: research

7. Additional structural chromosomal abnormalities have a negative prognostic effect in patients with inv(16)/t(16;16) acute myeloid leukemia (AML)
This study included 264 inv(16)/t(16;16)/CBFB-MYH11 AML patients (M/F  = 148/116; median age: 49, range 2-89 years). During a median follow-up of 34 months (range 1-190 months), 82 patients died, 169 achieved a complete remission and 13 had a partial response. Among 234 patients with abnormal karyotype, 218 had inv(16)(p13q22) and 16 had t(16;16)(p13;q22); and 110 (47%) had inv(16)/t(16;16) as the sole abnormality (Group A), 72 (30.8%) had one additional abnormality (Group B), and 52 (22.2%) had two or more abnormalities (complex karyotype, Group C). (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - April 1, 2019 Category: Genetics & Stem Cells Authors: Zhenya Tang, Pei Zhao, Wei Wang, Jun Gu, Keyur P. Patel, Chi Y. Ok, Gokce A. Toruner, Joseph Khoury, L. Jeffrey Medeiros, Guilin Tang Source Type: research

8. Mate pair sequencing characterization of 5q/7q co-deleted acute myeloid leukemia: a prospective study to discover novel co-abnormalities in complex karyotypes
Acute myeloid leukemia (AML) with myelodysplasia-related changes often is associated with a poor prognosis, particularly in the presence of deletions of the long arms of chromosomes 5 and 7. When these deletions co-occur, overall genomic profiles tend to harbor a higher number of structural rearrangements compared to other AML subtypes, and have thus been frequently categorized as having a “complex karyotype” by conventional cytogenetics. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - April 1, 2019 Category: Genetics & Stem Cells Authors: Beth Pitel, Cinthya Zepeda-Mendoza, Stephanie Smoley, Kathryn Pearce, Ivy Luoma, Roman Zenka, Rhett Ketterling, Nicole Hoppman, Jess Peterson, Patricia Greipp, Linda Baughn Source Type: research

9. Next generation sequencing for myeloid neoplasms: a diagnostic management team approach
The hematopathology Diagnostic Management Team (DMT) utilizes decision-support algorithms to guide test ordering for bone marrow biopsies. Although next-generation sequencing (NGS) testing is commonly available for myeloid malignancies, there is little guidance on optimal utilization in the diagnosis and management of these diseases. We have incorporated marrow morphology into DMT algorithms for NGS testing, recommending testing only if there is morphologic evidence of disease at diagnosis or first presentation, transformation, or relapse. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - April 1, 2019 Category: Genetics & Stem Cells Authors: Adam Seegmiller Source Type: research

10. The Spectrum of NTRK Fusion-associated Pediatric Tumors
Introduction: NTRK fusions have been described as oncogenic drivers in pediatric mesenchymal tumors. With the increasing use of NGS technology, the spectrum of NTRK fusion associated tumors is expanding. The FDA approval of Larotrectinib, a TRK inhibitor, for adult and pediatric solid tumors with NTRK fusions makes screening for NTRK fusions critical for patient care. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - April 1, 2019 Category: Genetics & Stem Cells Authors: Xiaonan Zhao, Fumin Lin, Lea Surrey, Minjie Luo, Andrew Bauer, Portia Kreiger, Bruce Pawel, Jennifer Pogoriler, Pierre Russo, Mariarita Santi, Marilyn Li Source Type: research

11. MCG 2.0: A highly curated, scalable precision cancer medicine resource
Identification of genetic abnormalities has become an important component of cancer diagnosis, risk stratification, and treatment planning, and many types of advanced or metastatic cancers are now routinely sequenced to identify mutations that may confer drug sensitivity or resistance. However, evaluating the clinical significance of the alterations identified by these assays can be difficult, especially as assays expand to characterize increasing amounts of genetic material. My Cancer Genome was initially launched in 2011 by the Vanderbilt-Ingram Cancer Center as the first web-based precision cancer medicine knowledge sou...
Source: Cancer Genetics and Cytogenetics - April 1, 2019 Category: Genetics & Stem Cells Authors: Marilyn Holt, Christine Micheel, Ingrid Anderson, Michele LeNoue-Newton, Neha Jain, Clinton Miller, Michelle Botyrius, Ian Maurer, Justin Yeakley, Lori Vanelli, Mia Levy Source Type: research