A new dual translocation of chromosome 14 in a pediatric Burkitt lymphoma/leukemia patient: t(8;14) and t(14;15)
Burkitt lymphoma (BL), including its leukemic counterpart Burkitt leukemia ( ≥25% bone marrow involvement), is an aggressive mature B-cell malignancy, characterized by specific histopathological, immunophenotypic and genetic features [1]. It is uncommon in adults but frequent in children and adolescents. BL together with its leukemic form is named Burkitt lymphoma/leukemia (BL/L). Cases presenting a tumor mass at extranodal site with bone marrow involvement are considered stage IV disease, which is associated with a poor prognosis. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - October 23, 2021 Category: Genetics & Stem Cells Authors: Mariana Quatrin, Claudia Pasti, Silvina Romano, Bel én Iarossi, Vanesa Giménez, Virginia Schuttenberg, Alejandra Costa, Irma Slavutsky Tags: Short Communication Source Type: research

Clonal cytogenetic abnormalities in donor-derived cells after sex mismatched allogeneic stem cell transplantation
In patients who have undergone sex-mismatch allogeneic stem cell transplant (SCT), cytogenetic analysis can take advantage of this sex-difference between recipient and donor-derived cells. The main assumption of testing is that only donor-derived cells (opposite of recipient's genotypic sex) with normal karyotype will be observed in patients in complete remission. By contrast, recipient cells (same genotypic sex) with clonal cytogenetic abnormalities (CCA) will be observed if the patient is in relapse. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - October 19, 2021 Category: Genetics & Stem Cells Authors: Gokce A. Toruner, Beenu Thakral, Zhenya Tang, Guilin Tang, L. Jeffrey Medeiros, Betul Oran Source Type: research

The oncogenic roles of NTRK fusions and methods of molecular diagnosis
The neurotrophic tyrosine receptor kinase (NTRK) genes encode a class of tropomyosin-receptor kinase (TRK) receptors that have critical roles in cell survival, proliferation, and differentiation. Chromosomal rearrangements involving the NTRK genes lead to gene fusions that are long known as oncogenic drivers of many tumors. These fusions are now recognized to be clinically actionable with both diagnostic and therapeutic significance. With the invention of TRK inhibition therapy, detection of NTRK fusions in tumor specimens has become critical for tumors potentially harboring NTRK fusions. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - October 17, 2021 Category: Genetics & Stem Cells Authors: Erfan Aref-Eshghi, Fumin Lin, Marilyn M. Li, Yiming Zhong Source Type: research

Molecular profiling of osteosarcoma in children and adolescents from different age groups using a next-generation sequencing panel
Osteosarcoma (OS) is the most common primary bone tumor among children and adolescents, with a peak of incidence in the second decade of life, during the pubertal growth spurt. OS is also characterized by its high risk of metastasis, with approximately 10% to 20% of patients presenting metastatic disease at diagnosis, the lung being the most common site; however, some patients may also develop bone and soft tissue metastasis [1]. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - October 4, 2021 Category: Genetics & Stem Cells Authors: G.M. Guimar ães, F. Tesser-Gamba, A.S. Petrilli, C.R.P. Donato-Macedo, M.T.S. Alves, F.T. de Lima, R.J. Garcia-Filho, R. Oliveira, S.R.C. Toledo Source Type: research

Genotype-Cancer Association in Patients with Fanconi Anemia due to Pathogenic Variants in FANCD1 (BRCA2) or FANCN (PALB2)
Fanconi anemia (FA) is a rare inherited bone marrow failure and cancer predisposition syndrome associated with defective DNA repair. Many patients with FA have characteristic birth defects, bone marrow failure and a dramatically high risk of cancer. Most patients have biallelic (homozygous or compound heterozygous) inheritance of pathogenic variants in one of at least 22 FA/BRCA DNA repair pathway genes; FANCB is X-linked recessive and FANCR is autosomal dominant [1]. FANCA is the most frequently mutated gene, followed by FANCC and FANCG [1]. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - October 4, 2021 Category: Genetics & Stem Cells Authors: Lisa J. McReynolds, Kajal Biswas, Neelam Giri, Shyam K. Sharan, Blanche P. Alter Source Type: research

Selection for or against Escape from Nonsense Mediated Decay is a Novel Signature for the Detection of Cancer Genes
Variants that cause new predicted termination codons (PTC), such as frameshift indels and stopgain point mutations (PTC+ variants), normally result in nonsense-mediated mRNA decay (NMD) prior to translation (NMD+) [1]. However, termination codons within 55bp of the final exon-exon junction or within the final exon can escape NMD (NMD-) and result in a truncated or extended peptide. Somatic NMD- variants are known to affect immunogenicity in some tumor types [2], and the ratio of somatic PTC+ variants that are NMD+ or NMD- varies between tumor suppressors and oncogenes due to positive and negative selection on NMD+ variants...
Source: Cancer Genetics and Cytogenetics - September 22, 2021 Category: Genetics & Stem Cells Authors: Runjun D. Kumar, Briana A. Burns, Paul J. Vandeventer, Pamela N. Luna, Chad A. Shaw Source Type: research

TERT gene rearrangement in chordomas and comparison to other TERT-rearranged solid tumors
Chordomas are rare, slow-growing neoplasms thought to arise from the foetal notochord remnant. A limited number of studies that examined the mutational profiles in chordomas identified potential driver mutations, including duplication in the TBXT gene (encoding brachyury), mutations in the PI3K/Akt signaling pathway, and loss of the CDKN2A gene. Most chordomas remain without clear driver mutations, and no fusion genes have been identified thus far. We discovered a novel TERT in-frame fusion involving RPH3AL (exon 5) and TERT (exon 2) in the index chordoma case. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - September 18, 2021 Category: Genetics & Stem Cells Authors: Ju- Yoon, Wei Jiang, Christopher R. Orr, Chase Rushton, Stacey Gargano, Sharon J. Song, Mitul Modi, Bryan Hozack, John Abraham, Atrayee Basu Mallick, John S.J. Brooks, Jason N. Rosenbaum, Paul J. Zhang Source Type: research

A Rare Case of Atypical Chronic Myeloid Leukemia Associated with t(8;22)(p11.2;q11.2)/ BCR-FGFR1 Rearrangement: A Case Report and Literature Review.
Originally designated the 8p11 myeloproliferative syndrome, the rare myeloid and/or lymphoid neoplasms characterized by translocations involving the fibroblast growth factor receptor-1 (FGFR1) gene at chromosome 8p11.2, are currently classified by the World Health Organization (WHO) under the term “myeloid/lymphoid neoplasms with FGFR1 rearrangement.1” This diagnostic subgroup is associated with heterogeneous disease manifestations including myeloid hyperplasia with eosinophilia, a high risk of progression to acute myeloid leukemia, and lymph node involvement by T- or B-lymphoblastic lymp homa. (Source: Cancer ...
Source: Cancer Genetics and Cytogenetics - September 13, 2021 Category: Genetics & Stem Cells Authors: Erik Washburn, Michael G. Bayerl, Rhett P. Ketterling, Jozef Malysz Source Type: research

Multi-region sequencing reveals genetic correlation between esophageal squamous cell carcinoma and matched cell-free DNA
Esophageal cancer is an aggressive and deadly form of malignancy that accounts for more than 4 million deaths every year, which has become a major global public health challenge. It can be divided into 2 major subtypes: esophageal adenocarcinoma (EAC) and esophageal squamous-cell carcinoma (ESCC). These two subtypes differ greatly with regard to their cell-of-origin patterns, risk factors, incidence rates and molecular mechanisms, but their survival outcomes ( ∼15%) are relatively the same [1, 2]. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - August 30, 2021 Category: Genetics & Stem Cells Authors: Zuyang Yuan, Xinfeng Wang, Xiao Geng, Yin Li, Fengwei Tan, Qi Xue, Shugeng Gao, Jie He Source Type: research

Novel genomic signature predictive of response to immune checkpoint blockade: A pan-cancer analysis from project Genomics Evidence Neoplasia Information Exchange (GENIE)
Immune checkpoint blockade (ICB) with agents that inhibit CTLA-4, programmed cell death protein 1 (PD-1), and programmed death-ligand 1 (PD-L1) has led to improvement in oncologic outcomes for patients with several different types of advanced-stage cancers [1-3]. Still, there is variability in ICB response, and there is a risk of significant treatment-related toxicity [4]. Therefore, identifying markers predictive of ICB response is of critical importance [5]. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - August 28, 2021 Category: Genetics & Stem Cells Authors: Nishwant Swami, William L. Hwang, Jimmy A. Guo, Hannah Hoffman, Matthew C. Abramowitz, Ziad Elbakouny, Himisha Beltran, Fallon Chipidza, Toni Choueiri, Alan Dal Pra, Franklin Huang, Salma Kaochar, Philip Kantoff, Daniel W. Kim, Amar U. Kishan, Erin Kobetz Source Type: research

Identification of variant APL translocations PRKAR1A-RAR α and ZBTB16-RARα (PLZF-RARα) through the MI-ONCOSEQ platform
The cornerstone of management in patients with acute promyelocytic leukemia (APL) is early diagnosis and prompt initiation of treatment with an all-trans retinoic acid (ATRA)-based regimen. Identification of the t(15;17)(PML-RARA) chromosomal translocation through conventional cytogenetics fluorescence in-situ hybridization (FISH) or detection of the promyelocytic leukemia-retinoic acid receptor alpha (PML-RAR α) fusion through RT-PCR represent the current standard of care for diagnosing APL. However, about 1-2% of patients with APL have a variant translocation involving other fusion partners with RARα besides ...
Source: Cancer Genetics and Cytogenetics - August 25, 2021 Category: Genetics & Stem Cells Authors: Darren King, Charles E. Foucar, Vincent Ma, Lydia Benitez-Colon, Anthony J. Perissinotti, Bernard Marini, Dan Robinson, Rupali Roy Bhave, Dale Bixby Source Type: research

When cascade testing for familial variant seems inadequate to provide clinically actionable information for blood relatives
Dear Editor, (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - August 24, 2021 Category: Genetics & Stem Cells Authors: Paraskevi Apostolou, Florentia Fostira, George Fountzilas, Evangelia Razis, Drakoulis Yannoukakos, Irene Konstantopoulou Source Type: research

Identification and Prevalence of Potentially Therapeutic Targetable Variants of Major Cancer Driver Genes in Ampullary Cancer Patients in India through Deep Sequencing
Ampullary cancer (AC) originates from the ampulla of vater, which is formed by convergence of the epithelium of distal common bile duct (CBD), pancreatic duct and duodenum [1]. Tumors originating from ampulla have been classified as intra-ampullary (intra-ampullary papillary tubular, intra-ampullary ductal), periampullary duodenal and ampullary NOS type depending on the site of origin of tumor [2]. The prevalence of AC varies in different parts of the world having higher incidence in India and China while United States and Australia show higher incidence of cancer of head of pancreas (CaHOP) [3-6]. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - August 14, 2021 Category: Genetics & Stem Cells Authors: Mr. Shravan Kumar Mishra, Prof Niraj Kumari, Prof Narendra Krishnani, Prof Rajneesh Kumar Singh, Prof Samir Mohindra Source Type: research

Germline mutation in the NBR1 gene involved in autophagy detected in a family with renal tumors
With more than 400,000 new cases diagnosed and 175,000 deaths each year worldwide, kidney cancer is the 14th most common cancer [1]. Renal Cell Carcinomas (RCC), whose major histological subtypes are clear-cell (ccRCC 75%), papillary (pRCC 15%) and chromophobe (chRCC 5%) carcinomas, account for 90-95% of all kidney tumors. Among other subtypes of tumors, angiomyolipomas (AML) are the most frequent mesenchymal tumors [2, 3]. Renal tumors can occur in a familial context, usually transmitted in an autosomal dominant mode. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - August 9, 2021 Category: Genetics & Stem Cells Authors: Florine Adolphe, Sophie Ferlicot, Virginie Verkarre, Katia Posseme, Sophie Couv é, Pauline Garnier, Nathalie Droin, Marc Deloger, Bastien Job, Sophie Giraud, Brigitte Bressac-de Paillerets, Betty Gardie, Stéphane Richard, Flore Renaud, Sophie Gad Source Type: research

Exosomal DNMT1 mRNA Transcript is Elevated in Acute Lymphoblastic Leukemia which might Reprograms Leukemia Progression
DNMT1 is an enzyme which catalyzes and transfers methyl groups to specific CpG fragments in DNA, and this process is defined as DNA methylation, DNMT1 was cloned by DNMT1 gene [1]. The major responsibility of DNMT1 is maintenance of DNA methylation and regulation of epigenetics [2]. Epigenetic factors (DNA methylation, gene regulation, and chromatin remodeling) contribute to predominant role in acute lymphoblastic leukemia (ALL) development and progression [3-5]. Dysregulated expression of DNMT1 causes aberrant DNA methylation which ultimately leads to tumors and abnormalities in normal developmental process [6, 7]. (Sourc...
Source: Cancer Genetics and Cytogenetics - August 2, 2021 Category: Genetics & Stem Cells Authors: Shabirul Haque, Sarah R. Vaiselbuh Source Type: research

Lynch Syndrome: Further Defining the Pediatric Spectrum
Lynch syndrome (LS) is an autosomal dominant cancer predisposition syndrome defined molecularly by the presence of a heterozygous pathogenic variant in one of the mismatch repair (MMR) genes:  MLH1, MSH2, MSH6, PMS2, or EPCAM. The incidence of LS in the general population is estimated at 1 in 279, with an even higher incidence in those with colorectal (1:35 or 3%) or endometrial cancer (1:56, 1.8%), the two most common Lynch-associated cancers [1]. Monoallelic pathogenic variants in MM R genes also increase an individual's risk for uterine, ovarian, stomach, urothelial, small bowel, pancreas, and biliary tract ca...
Source: Cancer Genetics and Cytogenetics - July 25, 2021 Category: Genetics & Stem Cells Authors: Chelsea Self, Alexandra Suttman, Kami Schneider, Lindsey Hoffman Source Type: research

A novel ATRX splice variant causing acquired HbH disease in myelodysplastic syndrome with excess blasts-1
A 60-year-old male with myelodysplastic syndrome with excess blasts-I had unexplained microcytic hypochromic anemia. This was revealed on supravital staining, hemoglobin studies and next-generation sequencing to be caused by a novel hemizygous potentially pathogenic missense/splice site variant NM_000489.5:c.6848A>C, (p.Lys2283Thr) in exon 31 of the ATRX gene. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - July 19, 2021 Category: Genetics & Stem Cells Authors: Nabhajit Mallik, Namrata Singh, Manu Jamwal, Sanjeev Chhabra, Jasbir Kaur Hira, Pankaj Malhotra, Reena Das, Prashant Sharma Tags: Case Reports for Cancer Curation Source Type: research

Longitudinal change of genetic variations in cetuximab-treated metastatic colorectal cancer
Colorectal cancer (CRC) is the third most common malignancy and the second-leading cause of cancer-related deaths; moreover, it markedly affects global public health [1]. Although immune checkpoint inhibitors have improved the survival rate of various cancer types, majority of CRC types —in particular microsatellite-stable type—do not respond effectively to immunotherapy [2]. Considering that several recently developed targeted agents failed to prove their efficacy in metastatic colorectal cancer (mCRC), future clinical studies are required to explore novel therapeutic agents i n this area [3, 4]. (Source: Canc...
Source: Cancer Genetics and Cytogenetics - July 10, 2021 Category: Genetics & Stem Cells Authors: Sun Young Kim, Kwoneel Kim, Su Han Cho, Sung-Min Chun, Eunyoung Tak, Yong Sang Hong, Jeong Eun Kim, Tae Won Kim Source Type: research

Editorial Board
(Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - July 7, 2021 Category: Genetics & Stem Cells Source Type: research

Identification of KMT2A-ARHGEF12 fusion in a child with a high-grade B-cell lymphoma
We present a 12-year-old boy with high-grade B-cell lymphoma and KMT2A-ARHGEF12 fusion, whose clinical, morphologic, phenotypic and genotypic profile is strikingly similar to the other case of high grade B cell lymphoma, both otherwise perfectly mimicking Burkitt lymphoma. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - June 26, 2021 Category: Genetics & Stem Cells Authors: Kristian T. Schafernak, James A. Williams, Benjamin I. Clyde, Chelsea Marcus, Brennan Decker, Reha M. Toydemir Source Type: research

Concomitance of a novel RMDN2-ALK fusion and an EML4-ALK fusion in a lung adenocarcinoma
Lung cancer is a common malignancy and a prominent cause of cancer mortality in the world [1]. Although lung cancer remains associated with a very poor prognosis, gene fusions/rearrangements have been shown to be important therapeutic targets in the treatment of advanced stage non-small cell lung cancer (NSCLC) [2-5]. The anaplastic lymphoma kinase (ALK) gene encodes a transmembrane tyrosine kinase receptor. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - June 22, 2021 Category: Genetics & Stem Cells Authors: Liqun Jiang, Suping Chen, Victoria Stinnett, Lisa Haley, Laura Morsberger, Alison Shane, Melanie Hardy, Kirstin Smith, Christopher D. Gocke, Ming-Tseh Lin, Ying S. Zou Source Type: research

A pediatric bal case with double ph chromosomes and trisomy 5
Biphenotypic acute leukemias (BAL) or mixed phenotype acute leukemia (MPAL) are an extremely heterogeneous type of leukemia in terms of immunophenotype and genetics. In biphenotypic acute leukemias, blasts express both myeloid and lymphoid markers and BAL is clinically worse than both acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) [1]. BAL is observed in 2-3% of childhood acute leukemia, and there is no optimal treatment option yet. The most common chromosomal anomalies (15%) in BAL are MLL gene rearrangements and BCR/ABL fusion genes. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - June 21, 2021 Category: Genetics & Stem Cells Authors: Gulcin GUNDEN, Sevgi ISIK, Canan OZDEMIR, Oguz C İLİNGİR, Ozcan BOR, Ebru ERZURUMLUOGLU GOKALP, Sinem KOCAGIL, Sevilhan ARTAN, Beyhan DURAK ARAS Tags: CASE REPORT Source Type: research

BRCA1 and BRCA2 whole cDNA analysis in unsolved hereditary breast/ovarian cancer patients
Germline pathogenic variants in the tumour suppressor genes BRCA1 and BRCA2 (BRCA1/2) confer high risks of developing breast/ovarian cancer. Since the discovery of these genes in the early 1990s, BRCA1/2 genetic testing has been offered to an increasing number of hereditary breast/ovarian cancer (HBOC) patients and families due to its proven clinical benefits. However, only a proportion of HBOC families are explained by deleterious variants in these genes and about 40-50% of the cases remain unresolved [1 –3]. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - June 17, 2021 Category: Genetics & Stem Cells Authors: Gemma Montalban, Sandra Bonache, Vanessa Bach, Alexandra Gisbert-Beamud, Anna Ten és, Alejandro Moles-Fernández, Adrià López-Fernández, Estela Carrasco, Judith Balmaña, Orland Diez, Sara Gutiérrez-Enríquez Source Type: research

Mutations in BRCA-related breast and ovarian cancer in the South African Indian population: a descriptive study
The Indian population from mainland India is an admixture of people representing different cultures, castes and religions. It also includes groups of people traditionally not affiliated with India, such as those of European, Arabic, African and Asian descent [1]. An attempt by Roychoudhury et al. [2] to classify this unique population was unsuccessful, as the authors concluded that this population was an admixture of subcultures from within and outside of India. Padayachee and Morrell [3] indicated that the South African (SA) Indian population is an admixture of individuals from mainland India, neighbouring countries such ...
Source: Cancer Genetics and Cytogenetics - June 14, 2021 Category: Genetics & Stem Cells Authors: Herkulaas MVE Combrink, Jaco Oosthuizen, Botma Visser, Namitha Chabilal, Ines Buccimazza, William D Foulkes, Nerina C van der Merwe Tags: Original Article Source Type: research

Molecular follow-up of first-line treatment by osimertinib in lung cancer: importance of using appropriate tools for detecting EGFR resistance mutation C797S
Tyrosine kinase inhibitors (TKI) targeting the epidermal growth factor receptor (EGFR) have dramatically improved the response rate and progression free survival (PFS) of patients with EGFR-mutated non-small cell lung carcinoma (NSCLC) [1]. Detection of alterations in the DNA sequence of exons 18-21 of EGFR are currently done by molecular biology platforms worldwide in order to identify patients who will strongly benefit from such a treatment. Notably, small in-frame deletions in exon 19 and point mutations in exon 21, such as L858R, are the most frequent predictive biomarkers of response. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - June 9, 2021 Category: Genetics & Stem Cells Authors: Y. Fanjat, H. Barazzutti, I. Di Mauro, L. Tabary Martin, V. Duranton-Tanneur, S. Gimet, H. B érard, F. Pedeutour Tags: BRIEF COMMUNICATION Source Type: research

Whole-exome sequencing in osteosarcoma with distinct prognosis reveals disparate genetic heterogeneity
Osteosarcoma (OS) is the most common primary malignant bone cancer, with incidence of 2 ∼3 cases per million in children and adolescents, bone cancer is one of the five most common malignant tumor causes of death among adolescents [1]. Many subtypes of OS have been described in the 2013 World Health Organization classification, the most common of which is conventional OS [2]. However , the biological behaviors of OS tumors are quite different, even within the same subtype. Following chemotherapeutic and surgical treatment, some patients don't experience recurrence or metastasis, and ultimately achieve complete disease ...
Source: Cancer Genetics and Cytogenetics - June 8, 2021 Category: Genetics & Stem Cells Authors: Weifeng Liu, Renxian Wang, Yanrui Zhang, Huina Wang, Zhen Huang, Tao Jin, Yongkun Yang, Yang Sun, Shanbo Cao, Xiaohui Niu Source Type: research

Long-read nanopore sequencing enables accurate confirmation of a recurrent PMS2 insertion –deletion variant located in a region of complex genomic architecture
Massively parallel short-read “next generation” sequencing (NGS) has become the principal first-line screening approach for the molecular diagnosis of inherited disorders [1]. For genetically heterogeneous conditions, NGS permits concurrent (rather than consecutive) analysis of disease-associated genes. In Lynch syndrome (OM IM: 120435), an autosomal dominant disorder associated with predisposition to colorectal cancer, these include the DNA mismatch repair genes MSH2, MSH6, MLH1 and PMS2. The genomic targets for sequencing may be chosen using any of a small range of laboratory workflows. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - May 28, 2021 Category: Genetics & Stem Cells Authors: Christopher M. Watson, Laura A. Crinnion, Jennifer Simmonds, Nick Camm, Julian Adlard, David T. Bonthron Tags: Short Communication Source Type: research

A melanoma patient with macrophage-cancer cell hybrids in the primary tumor, a lymph node metastasis and a brain metastasis.
In 1911, German gynecologist Prof. Otto Aichel made the remarkable proposal that metastasis occurs following leucocyte-tumor cell fusion and hybrid formation. He stated that a new hybrid cell would form with traits of both “mother cells”1. Today, that would refer to gene expression patterns from both fusion partners in the same hybrid cell. At least some hybrids would express the leukocytic traits of motility, chemotaxis and homing along with the de-regulated cell division of the cancer cell. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - May 28, 2021 Category: Genetics & Stem Cells Authors: Greggory S. LaBerge, Eric Duvall, Zachary Grasmick, Kay Haedicke, Anjela Galan, John Pawelek Source Type: research

EML4-ALK fusion variant.3 and co-occurrent PIK3CA E542K mutation exhibiting primary resistance to three generations of ALK inhibitors
The ALK inhibitors are promising therapeutic agents against lung cancer harboring ALK fusion genes and are currently under development up to the third generation. However, its therapeutic effects are reported to be affected by differences in ALK variants and co-occurrent mutations. Materials and Methods; We experienced an autopsy case of an ALK-positive lung cancer patient who showed primary resistance to three generations of ALK inhibitors. The poor survival time of the case was 14 months. To reveal the mechanism of primary resistance to three generations of ALK inhibitors, we performed next generation sequencing for 12 s...
Source: Cancer Genetics and Cytogenetics - May 28, 2021 Category: Genetics & Stem Cells Authors: Kei Kunimasa, Yosuke Hirotsu, Yoji Kukita, Yumi Ueda, Yoshiharu Sato, Madoka Kimura, Tomoyuki Otsuka, Yuichiro Hamamoto, Motohiro Tamiya, Takako Inoue, Takahisa Kawamura, Kazumi Nishino, Kenji Amemiya, Taichiro Goto, Hitoshi Mochizuki, Keiichiro Honma, Ma Tags: Case Report Source Type: research

Copy Number Alterations Identify a Smoking-Associated Expression Signature Predictive of Poor Outcome in Head and Neck Squamous Cell Carcinoma
HNSCC is an aggressive neoplasm of the upper aerodigestive tract caused by exposure to tobacco, alcohol, and high-risk HPV infection (1,2). Over 66 000 new HNSCC cases and 14 500 deaths are predicted in the U.S. in 2021 (3) with five-year post-treatment survival near 65% (3). Cervical nodal metastasis is frequently found in HNSCC, and is an important prognostic indicator associated with late stage (American Joint Committee on Cancer (AJCC) stage III/IV) disease in aggressive smoking-associated HPV-negative cancers (4,5). (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - May 28, 2021 Category: Genetics & Stem Cells Authors: Brenen W. Papenberg, James Ingles, Si Gao, Jun Feng, Jessica L. Allen, Steven M. Markwell, Erik T. Interval, Phillip A. Montague, Sijin Wen, Scott A. Weed Source Type: research

Long-read nanopore sequencing enables accurate confirmation of a recurrent PMS2 insertion-deletion variant located in a region of complex genomic architecture.
Massively parallel short-read “next generation” sequencing (NGS) has become the principal first-line screening approach for the molecular diagnosis of inherited disorders [1]. For genetically heterogeneous conditions, NGS permits concurrent (rather than consecutive) analysis of disease-associated genes. In Lynch syndrome (OM IM: 120435), an autosomal dominant disorder associated with predisposition to colorectal cancer, these include the DNA mismatch repair genes MSH2, MSH6, MLH1 and PMS2. The genomic targets for sequencing may be chosen using any of a small range of laboratory workflows. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - May 28, 2021 Category: Genetics & Stem Cells Authors: Christopher M. Watson, Laura A. Crinnion, Jennifer Simmonds, Nick Camm, Julian Adlard, David T. Bonthron Source Type: research

Content of circulating tumor DNA depends on the tumor type and the dynamics of tumor size, but is not influenced significantly by physical exercise, time of the day or recent meal
The development of cancer always involves the acquisition of somatic mutations. When a critical mass of tumor volume is achieved, mutated tumor-derived DNA can often be detected in the plasma and other body liquids. The mechanism of tumor DNA shedding into the bloodstream is not entirely understood. It is believed, that dying tumors cells, which are destroyed by apoptosis, necrosis or other types of cell death, are the main source of circulating tumor DNA (ctDNA) [1, 2]. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - May 28, 2021 Category: Genetics & Stem Cells Authors: Ekaterina S. Kuligina, Roman Meerovich, Kirill A. Zagorodnev, Maxim M. Kholmatov, Tatyana N. Sokolova, Tatiana A. Laidus, Aleksandr A. Romanko, Aleksandr S. Martianov, Maria O. Anisimova, Olga A. Zaitseva, Olga S. Yatsuk, Grigoriy A. Yanus, Evgeny N. Imya Source Type: research

A Case report: Co-occurrence of IMAGe syndrome and Rhabdomyosarcoma
IMAGe syndrome is a rare congenital disorder, presenting with intrauterine growth restriction, metaphyseal dysplasia, adrenal hypoplasia congenita and genital anomalies (in males). So far only 17 individuals have been diagnosed molecularly with IMAGe syndrome, this patient is the first case of an individual diagnosed with IMAGe and concurrent rhabdomyosarcoma.The patient was born at 30 weeks ’ gestation and received treatment for hyponatremia and hyperkalemia. At 4 9/12 years of age the patient showed a painless, non-mobile mass on the left thigh. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - May 25, 2021 Category: Genetics & Stem Cells Authors: Maria Bolomiti, Erik B åtnes-Pedersen, Gabriela Telman, Danuta Januszkiewicz-Lewandowska Source Type: research

Differences in the Mitochondrial Microsatellite Instability of Keratoacanthoma and Cutaneous Squamous Cell Carcinoma
Keratoacanthoma (KA) is a common cutaneous neoplasm characterized by rapid, abundant growth and spontaneous resolution. These lesions usually regress over 4-6 months, with an expulsion of the keratin plug and resorption of the tumoral mass, leaving an atrophic, hypopigmented scar [1]. One study reported that about 20% of the population are expected to develop skin cancer during their lifetime [2]. In humans, naturally occurring KAs are categorized as solitary or multiple [3] and KA is typically de novo, but studies have reported its association with genetic diseases, inflammatory dermatoses, congenital skin lesions and sca...
Source: Cancer Genetics and Cytogenetics - May 25, 2021 Category: Genetics & Stem Cells Authors: Mohammad Rizwan Alam, Ahmad Alsulimani, Shafiul Haque, Hye Ra Jung, Jae-Ho Lee, Chang-Ho Jeon, Dae-Kwang Kim Source Type: research

A hereditary ovarian cancer family with rare pathogenic splicing mutation: implications for variant interpretation
Ovarian cancer (OC) is one of the most common malignancies and the second leading cause of death in gynecology. Owing to a lag in early detection and screening methods, the 5-year survival rate of OC is only about 46% [1, 2]. A large number of studies have shown that some cases of OC show familial inheritance. Women in this family are at much higher risk for ovarian, breast, peritoneal and other malignancies. Also known as familial/hereditary ovarian cancer syndrome (FHOCs), patients with FHOCs develop early and relapse quickly after treatment. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - May 25, 2021 Category: Genetics & Stem Cells Authors: Ke Wang, Yingnan Ye, Lewen Bao, Yanan Cheng, Yandong Cao, Jinpu Yu Tags: Case Report Source Type: research

Case report of a man with multiple paragangliomas and pathogenic germline variants in both NF1 and SDHD
We report the case of a patient with multiple head and neck paragangliomas and two pathogenic germline variants in susceptibility genes for this disease. Pheochromocytomas and paragangliomas (PPGLs) are neuroendocrine tumors with the highest degree of heritability of any other cancer type [1]. Pathogenic variants in about 20 genes are known to cause approximately 40% of cases [2]. Depending on the gene involved, important clinical characteristics such as malignancy and recurrence risks vary, while the different underlying tumorigenic mechanisms offer opportunities for personalized therapeutic approaches [3]. (Source: Cance...
Source: Cancer Genetics and Cytogenetics - May 24, 2021 Category: Genetics & Stem Cells Authors: Prodromos Chatzikyriakou, Dr. Philip Touska, Mufaddal T. Moonim, Mr. Rupert Obholzer, Dr. Shazia Afridi, Dr. Ann Sandison, Rebecca J. Oakey, Dr. Louise Izatt Source Type: research

Hereditary inflammatory fibroid polyps caused by germline pathogenic variants in PDGFRA: refining PDGFRA-mutation syndrome
A 35-year-old Filipino woman presented with epigastric pain and was found to have two large jejunal and ileal inflammatory fibroid polyps (IFPs) and dozens of subcentimeter small bowel submucosal nodules. Targeted exon sequencing of PDGFRA on the resected jejunum IFP identified a variant c.1664A>G that was subsequently confirmed in the germline. Family history was striking for three relatives with confirmed IFPs, including one with small bowel intussusception on five occasions. All relatives with IFPs were confirmed to have the same PDGFRA germline likely pathogenic variant, all were female, and all had IFPs by age 50 y...
Source: Cancer Genetics and Cytogenetics - May 24, 2021 Category: Genetics & Stem Cells Authors: Rachel Hodan, Gregory W. Charville, Uri Ladabaum Source Type: research

Mitochondrial DNA Polymorphisms and Biogenesis Genes in Primary and Metastatic Uveal Melanoma Cell Lines
Uveal melanoma (UM) is the most common primary intraocular malignancy in adults [1]. Although UMs can be associated with any uveal tract tissue, the most common locations are within the choroid and ciliary body (97 –98% of all UMs) and the remaining occur in the iris (2–3%). Irradiation with either proton beam or radioactive plaque is the primary treatment modality in UM patients and is usually associated with preservation of the eye. In a minority of patients, enucleation is necessary. However, overall su rvival with this tumor is still poor with a 5-year survival rate of only 82% [2]. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - May 18, 2021 Category: Genetics & Stem Cells Authors: Lata Singh, Shari R. Atilano, Martine J. Jager, M. Cristina Kenney Source Type: research

Therapy-Related Acute Myeloid Leukemia with KMT2A-SNX9 gene fusion associated with a hyperdiploid karyotype after Hemophagocytic Lymphohistiocytosis
Therapy-related acute myeloid leukemia (t-AML) following treatment with topoisomerase-II (topo-II) inhibitors has been increasingly reported and accounts for about 6.8% of AML [1]. The t-AML is a causal effect of somatic alterations after cytotoxic chemotherapy and/or radiotherapy, or even exposure to agents, such as anthracyclines and topo-II inhibitors (e.g. epipodophyllotoxins). Etoposide – a podophyllotoxin derivative – induces DNA strand breaks by inhibiting the action of topo-II and it is used in combination with other chemotherapeutic agents as first-line treatment of a variety of malignancies as well as...
Source: Cancer Genetics and Cytogenetics - May 6, 2021 Category: Genetics & Stem Cells Authors: Ingrid Sardou-Cezar, Bruno A. Lopes, Francianne Gomes Andrade, Teresa Cristina Cardoso Fonseca, Teresa de Souza Fernandez, Patrizia Larghero, Regiana Quinto de Souza, Gisele Loth, Lisandro Lima Ribeiro, Carmen Bonfim, Elissa Santos Morgado, Rolf Marschale Tags: Short Communication Source Type: research

High penetrance of myeloid neoplasia with diverse clinical and cytogenetic features in three siblings with a familial GATA2 deficiency
Pathogenic germ-line variants in GATA2 (GATA2-deficiency) can cause childhood myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML), and can be associated with distinct clinical syndromic features. However, penetrance and genotype-phenotype correlations are incompletely understood. Here we report on the clinically diverse features of three siblings affected by GATA2c.1021_1031del over an 18-year period, all initially presenting in childhood and adolescence with MDS and AML with monosomy 7 (-7), and one also with trisomy 8 (+8). (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - April 22, 2021 Category: Genetics & Stem Cells Authors: Jamie M. Ellingford, Nick Telford, Jill Urquhart, Andrew M Will, Denise Bonney, Ben Adams, Rachel Dixon, Bronwyn Kerr, Graeme CM Black, Robert F Wynn, Stefan Meyer Source Type: research

Ossifying low grade endometrial stromal sarcoma with PHF1-BRD8 fusion
Low grade endometrial stromal sarcomas (LG-ESS) are rare. They are composed of uniform, cellular, oval to spindle-shaped uterine mesenchymal cells of endometrial stromal type, surrounding a delicate network of spiral arterioles. Fibromyxoid variants have occasionally been reported.[1, 2] Before the identification of specific chromosomal translocations, CD10 protein expression detection was considered the most reliable marker of LG-ESS.[3] LG-ESS are known to contain a variety of unique genetic events. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - April 22, 2021 Category: Genetics & Stem Cells Authors: Paul Chih-Hsueh Chen, Hsuan-Ying Huang, Ming-Yi Chung, Chin-Chen Pan Source Type: research

Novel MET Exon 14 Skipping Analogs Characterized in Non-Small Cell Lung Cancer Patients: A Case Study
The MET gene, located at chromosome 7q21-q31, encodes the widely expressed receptor of hepatocyte growth factor (HGF), which is involved in various cellular processes, including cell growth, proliferation, survival, migration, and differentiation [1]. Gain-of-function alteration in MET is known as a primary oncogenic driver and a major factor for resistance to tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC) treatment [2-4]. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - April 16, 2021 Category: Genetics & Stem Cells Authors: Minke Shi, Jing Ma, Meilin Feng, Lei Liang, Hongyuan Chen, Tao Wang, Zhenghua Xie Source Type: research

Interpretative Differences of Combined Cytogenetic and Molecular Profiling Highlights Differences Between MRC and ELN classifications of AML
Prognosis of newly diagnosed acute myeloid leukemia (AML) is largely dependent on genetic features that are revealed through karyotype analysis. Roughly half of all diagnostic karyotypes demonstrate a chromosomal aberration that can be used to assess prognosis [1]. With the addition of sub-karyotypic mutations, AML includes a considerable number of unique malignancies and can even include heterogeneous clonal populations [2, 3]. There are a number of different prognostic categorization schemes for AML including those from the World Health Organization (WHO) [4], the National Comprehensive Cancer Network (NCCN) [5], Southwe...
Source: Cancer Genetics and Cytogenetics - April 15, 2021 Category: Genetics & Stem Cells Authors: Robyn T. Sussman, Bryan Manning, Daniel Ackerman, Ashkan Bigdeli, Paige Pammer, Priya D. Velu, Selina M. Luger, Adam Bagg, Martin Carroll, Jennifer J.D. Morrissette Source Type: research

Determination of the key ccRCC-related molecules from monolayer network to three-layer network
Renal cell carcinoma (RCC) is one of the most common cancers in men and women [1-3]. RCC accounts for 2-3% of all cancers and about 90% of kidney malignancies [4, 5]. Clear cell renal cell carcinoma (ccRCC) is the most ubiquitous subtype in RCC, accounting for 75% of kidney cases [4, 6, 7] and 4% of adult malignancies [8]. Nearly 40% of ccRCC may metastasize to other organs, including lungs, bones, brain and lymph nodes with increasing incidence [8-10]. Therefore, new insights into the pathogenesis of ccRCC will be conducive to diagnosis, treatment and prognosis. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - April 12, 2021 Category: Genetics & Stem Cells Authors: Yanyan Wu, Yanrui Ding, Jie Wang, Xiaxia Wang Tags: Original Article Source Type: research

Late recurrence of lung adenocarcinoma harboring EGFR exon 20 Insertion (A763_Y764insFQEA) mutation successfully treated with osimertinib
We present the case of a female patient with recurrent lung adenocarcinoma from a lung tumor resected 10 years earlier. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - April 10, 2021 Category: Genetics & Stem Cells Authors: Kei Kunimasa, Kazumi Nishino, Yoji Kukita, Shingo Matsumoto, Hayato Kawachi, Takahisa Kawamura, Takako Inoue, Motohiro Tamiya, Keiichiro Honma, Naotoshi Sugimoto, Tomoyuki Yamasaki, Fumio Imamura, Koichi Goto, Toru Kumagai Tags: Case Report Source Type: research

Rare and favorable prognosis of pediatric acute lymphoblastic leukemia with TLS-ERG fusion gene: case report with long-term follow-up and review of literature
Gene abnormalities, particularly chromosomal rearrangements generating gene fusion, are associated with clinical characteristics and prognosis of leukemia. Translocated in liposarcoma/fused in sarcoma (TLS) was discovered 20 years ago through a characteristic chromosomal translocation [1]. TLS-ERG fusion gene, also known as FUS-ERG fusion gene is formed by the translocation t(16;21)(p11;q22), which is a rare reciprocal chromosomal change most frequently observed in all French-American-British variants of acute myeloid leukemia (AML), except for M3 [2-6], and blast crisis of chronic myelocytic leukemia (CML) [7]. (Source: C...
Source: Cancer Genetics and Cytogenetics - April 10, 2021 Category: Genetics & Stem Cells Authors: Sisi Li, Wei Huang, Yuanyuan Wu, Xiaojun Xu, Chan Liao, Yongmin Tang Tags: Original Article Source Type: research

Identification of a Novel resistance ALK p.(Q1188_L1190del) deletion in a Patient with ALK-rearranged Non –small-cell Lung cancer
The prognosis of anaplastic lymphoma kinase (ALK) rearranged non small cell lung carcinoma (NSCLC) has significantly improved with newer generations of tyrosine kinase inhibitors (TKIs) [1]. There are five TKIs (Crizotinib, Ceritinib, Alectinib, Lorlatinib and Brigatinib), which are presently available for treating ALK positive NSCLC [2]. Currently Alectinib, which is a second generation TKI is standard of care in stage 4 ALK translocated NSCLC. Third generation TKIs like Lorlatinib and Brigatinib are recommended when secondary resistance develops. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - April 4, 2021 Category: Genetics & Stem Cells Authors: Moushumi Suryavanshi, Krushna Chaudhari, Shrinidhi Nathany, Vineet Talwar Source Type: research

The spectrum of tumors harboring BAP1 gene alterations
Germline pathogenic sequence variants (PSVs) in the BRCA1-associated protein (BAP1) gene (MIM # 603089) are associated with a rare inherited BAP1-related tumor predisposition syndrome (TPDS) (MIM # 614327). BAP1 PSVs confer a substantially increased risk for developing uveal (UM) and cutaneous melanoma (CM), pleural and peritoneal mesothelioma, and renal cell carcinoma (RCC), and an increased risk for developing other cancer types, including breast cancer (BC), albeit to a lesser extent [1 –3]. Somatic inactivation of the BAP1 gene is commonly encountered in TPDS-related tumors and, to a lesser degree, in other tumor...
Source: Cancer Genetics and Cytogenetics - April 4, 2021 Category: Genetics & Stem Cells Authors: Yael Laitman, Justin Newberg, Rinat Bernstein Molho, Dexter X. Jin, Eitan Friedman Source Type: research

Invasive ACTH-Producing Pituitary Gland Neoplasm Secondary to MSH2 Mutation
Germline mutations in mismatch repair (MMR) genes MSH2, MLH1, MSH6, PMS2 and EPCAM are responsible for Lynch syndrome, a hereditary cancer-predisposition disorder also known as hereditary non-polyposis colorectal cancer (HNPCC). These genes have roles in repairing errors in DNA that can arise during replication. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - April 4, 2021 Category: Genetics & Stem Cells Authors: PB Loughrey, G Baker, B Herron, S Cooke, D Iacovazzo, JR Lindsay, M Korbonits Source Type: research

Somatic NF1 mutations in pituitary adenomas: report of two cases
In this report, we describe two cases of pituitary adenomas with rare, somatic NF1 variants. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - April 1, 2021 Category: Genetics & Stem Cells Authors: Christopher S. Hong, Adam J. Kundishora, Aladine A. Elsamadicy, Andrew B. Koo, Declan McGuone, Silvio E. Inzucchi, Sacit Bulent Omay, E. Zeynep Erson-Omay Source Type: research