1. Microdeletion 13q12.2 in B cell acute lymphoblastic leukemia: Little but important!
Chromosomal microarray analysis (CMA) is instrumental for identification of recurrent focal deletions in patients with B cell acute lymphoblastic leukemia (B-ALL). These microdeletions include genes involved in B cell differentiation, cell cycle control and transcriptional regulation often with prognostic or therapeutic significance. Recently, a 13q12.2 microdeletion with breakpoints upstream of FLT3 and within intronic regions of the PAN3 gene was reported. Functionally, this microdeletion resulted in enhancer hijacking and constitutive activation of FLT3 in pediatric B-ALL. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - November 1, 2022 Category: Genetics & Stem Cells Authors: Daynna Wolff, Yassmine Akkari, Linda Baughn, Nicole Hoppman, John Herriges, Denise Quigley, Gordana Raca, Cynthia Schandl, Lina Shao, Iya Znoyko Source Type: research
2. Clinical, cytogenetic and genomic profiling of B-Other Acute Lymphoblastic Leukemia: An Indian cohort study
∼30% of B-ALL patients remain unclassified at the genetic level, lacking known cytogenetic aberrations and are arbitrarily grouped intermediate risk, B-other-ALL. Recently, recurrent genetic abnormalities have emerged within this heterogeneous subgroup replacing the default assignment of intermedi ate risk with definitive prognostic information. We prospectively analyzed 368 patients to establish the incidence and complete clinical, cytogenetic and molecular profile of B-Other ALL in India. Fluorescence in situ hybridization (FISH) and Targeted RNA sequencing was carried out for detecting ph like ALL aberrations involvin...
Source: Cancer Genetics and Cytogenetics - November 1, 2022 Category: Genetics & Stem Cells Authors: Dhanlaxmi Shetty, Purvi Mohanty, Hemani Jain, Prashant Tembhare, Nikhil Patkar, Papagudi Subramanian, Jayashree Thorat, Lingaraj Nayak, Anant Gokarn, Sachin Punatar, Hasmukh Jain, Bhausaheb Bagal, Shyam Srinivasan, Akanksha Chichra, Nirmalya Roy, Chetan D Source Type: research
3. Homologous Recombination DNA Repair Deficiency in Hematological Malignancies
Genomic instability due to homologous recombination repair deficiency (HRD) predicts adverse prognosis in ovarian/ breast cancer with favorable responses to PARP inhibitors. HRD is a measure of genomic scar (GS) signatures associated with loss-of-heterozygosity (LOH), telomeric allelic imbalance (TAI), and large-scale state transitions (LST), excluding aneuploidy. While aneuploidy is a known poor prognostic marker in hematological malignancies (HM), the significance of HRD has not been explored. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - November 1, 2022 Category: Genetics & Stem Cells Authors: Ha Nguyen, Sherin Raju, Nazneen Ahmed, Diana Rush, Mark Dubina, Hector Alvarez, Anthony San Lucas, Zhenya Tang, Bedia Barkoh, Hyvan Dang, James Ozenci, Simi Puthooran, Peter Hu, Awdhesh Kalia, Christopher Bowman, Luthra Rajyalakshmi, Rashmi Kanagal-Shaman Source Type: research
4. Integrated genetic risk assessment in De-novo Acute Myeloid Leukemia in children and young adults
In July, 2020, a new therapeutic trial for pediatric de-novo AML (AAML1831) opened for enrollment in Children's Oncology Group. The trial utilizes integrated cytogenetic, FISH, and DNA and RNA sequencing data for the purpose of risk stratification and determination of therapy. There are 17 genetic findings that are designated as high risk for which therapy includes hematopoietic stem cell transplant, and four genetic findings that are designated as low risk for which therapy includes chemotherapy only (in the absence of minimal residual disease) . (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - November 1, 2022 Category: Genetics & Stem Cells Authors: Betsy Hirsch, Todd Cooper, Jessica Pollard, Todd Alonzo, Soheil Meschinchi, Wendy Lee, Matthew Kutny, E. Anders Kolb, Gordana Raca Source Type: research
5. IDH1 R132H, IDH2 R172K and BRAF V600E mutation detection by OncoScan CNV Plus in brain tumors
The OncoScan CNV Plus (OC+) assay is a single-nucleotide polymorphism-based microarray designed to detect genome-wide copy-number imbalance and loss of heterozygosity. This assay is also designed to detect 64 mutations in 9 cancer genes (BRAF, EGFR, IDH1, IDH2, KRAS, NRAS, PIK3CA, PTEN and TP53). We evaluated the accuracy of OC+ mutation calling in comparison to mutation testing by a 118-gene targeted amplicon-based neuro-oncology next-generation sequencing (NGS) panel for three brain tumor clinically relevant mutations: IDH1 R132H, IDH2 R172K and BRAF V600E. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - November 1, 2022 Category: Genetics & Stem Cells Authors: Lauren Choate, Beth Pitel, Corinne Praska, Thomas Kollmeyer, Robert Jenkins, Cristiane Ida Source Type: research
6. The clinical implications of polyploidy in oligodendrogliomas
Oligodendrogliomas are characterized by IDH mutation and whole-arm chromosome 1p/19q co-deletion. Polysomy chromosomes 1q/19p, detected by FISH, has been associated with earlier tumor recurrence and shorter survival. We retrospectively reviewed 58 oligodendroglioma cases tested at our institution, to assess the genome-wide copy number aberrations (CNAs) and mutational profiling. We compared previously identified high-risk genomic alterations between the polyploid and diploid groups, including mutations of NOTCH1, PIK3CA, PIK3R1, homozygous loss of CDKN2A/B, loss of 14q/15q, and gains of 7p/11p. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - November 1, 2022 Category: Genetics & Stem Cells Authors: Ching-Hua Liu, Matthew McCord, Pouya Jamshidi, Madina Sukhanova, Xinyan Lu Source Type: research
7. Overview of recurrent and novel gene fusions detected in a clinical diagnostic laboratory
Gene fusions are important mechanism of tumorigenesis, present in a wide range of neoplastic disorders and frequently impacting diagnosis, prognosis and therapy.The clinical use of Next Generation Sequencing technologies has enabled the identification of known and novel gene fusions with variable impact in patient care.The aim of this study is to present an overview of the gene fusions detected in a cohort of patients with solid tumors sequenced in a clinical diagnostic laboratory and to discuss the process of fusion curation for clinical purposes. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - November 1, 2022 Category: Genetics & Stem Cells Authors: Paulo Campregher, Larissa Lima, Caroline Silveira, Susana Rosa, Priscila Higaki, Joice Rosa, Karla Pelegrino, Jo ão Filho Source Type: research
8. Harnessing the power of microarray in the analysis of rarer pediatric sarcomas
A heterogeneous group (>80 tumor types), sarcomas are uncommon in any age group with ∼1% overall incidence. There is a relatively increased frequency in those (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - November 1, 2022 Category: Genetics & Stem Cells Authors: Maxine Sutcliffe, Ashley Robinson, Stephanie Smith, Rodolfo Ortega, Sara Gellatly, Fariborz Rashid-Kolvear Source Type: research
9. The dual PI3K inhibitor duvelisib potently inhibits cytokine release syndrome while maintaining CAR-T function
Clinical efficacy of CAR-T is limited by toxicities such as Cytokine Release Syndrome (CRS) in over 30% of patients. Using a protein kinase inhibitor library, we identified duvelisib, a novel and selective dual PI3K inhibitor as a potent inhibitor of CRS in vitro and in vivo without attenuating CAR-T function. To study the mechanisms of inhibition of CRS, CART19 (19-28BB?), CD19+ Ramos CBR GFP (CG), and immature dendritic cells (IDC) were co-cultured with duvelisib and ruxolitinib (JAK1/2 inhibitor; a less potent inhibitor of CRS also identified in screen) and submitted for scRNA-seq. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - November 1, 2022 Category: Genetics & Stem Cells Authors: Parmeshwar Amatya, Alun Carter, Julie Ritchey, Reyka Jayasinghe, Matthew Cooper, Jonathan Pachter, John Dipersio Source Type: research
10. HLA class II Immunogenic Mutation Burden predicts response to immune checkpoint blockade
HLA class I immunogenic mutations (IMM) have been previously studied as prognostic biomarkers for immune-checkpoint blockade (ICB) treatments, while HLA class II IMMs remain unexplored. We characterized the impact of HLA class II restricted IMMs on prognosis by analyzing the HLA class II IMM landscape of four ICB-treated cohorts in non-small cell lung cancer (NSCLC)(n=123) and melanoma (n=110). Using MHCnuggets, a neural-network based model, and whole-exome sequencing data, we identified 5,639 HLA class II IMMs across the four cohorts. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - November 1, 2022 Category: Genetics & Stem Cells Authors: Xiaoshan Shao, Justin Huang, Noushin Niknafs, Archana Balan, Christopher Cherry, James White, Victor Velculescu, Valsamo Anagnostou, Rachel Karchin Source Type: research
11. The complex nature of variant interactions in cancer requires updates to variant interpretation resources
CIViC, the Clinical Interpretation of Variants in Cancer knowledgebase (www.civicdb.org), has provided structured data and an open-access curation interface to enable scientists and other community stakeholders to curate variant information from published literature since 2014. Since then, CIViC has continued to evolve to incorporate new community guidelines and user feedback. CIViC has been embraced by the community with>300 contributors submitting content that represents>3100 publications,>450 genes, and>3000 variants, and become the official knowledgebase supporting somatic cancer variant curation efforts for ClinGen. (...
Source: Cancer Genetics and Cytogenetics - November 1, 2022 Category: Genetics & Stem Cells Authors: Kilannin Krysiak, Susanna Kiwala, Adam C. Coffman, Joshua F. McMichael, Arpad M. Danos, Jason Saliba, Cameron J. Grisdale, Jake Lever, Lana Sheta, Shruti Rao, Alex H. Wagner, Malachi Griffith, Obi L. Griffith Source Type: research
12. Expanding clinical actionability in individual patient profiles with the Molecular Oncology Almanac
MOAlmanac is an open source clinical interpretation algorithm and paired knowledge base for precision cancer medicine used to rapidly characterize and identify genomic features related to therapeutic sensitivity and resistance and of prognostic relevance. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - November 1, 2022 Category: Genetics & Stem Cells Authors: Brendan Reardon, Eliezer Van Allen Source Type: research
13. Implementation of new ClinGen/CGC/VICC recommendations for classification of oncogenicity of somatic variants using AI
The ClinGen, CGC and VICC recently published new recommendations for the classification of pathogenicity of somatic variants in cancer, in order to create a set of standards when classifying the oncogenicity of a somatic variant. While the detailed evaluation criteria will increase classification consistency between different labs, the process is time-consuming and holds some computational challenges. Here, we present a novel AI-based oncogenicity classification engine for somatic variants based on these new recommendations and integrated it into Franklin (franklin.genoox.com), an open-access platform for variant interpret...
Source: Cancer Genetics and Cytogenetics - November 1, 2022 Category: Genetics & Stem Cells Authors: Yaron Einhorn, Moshe Einhorn, Yaron Assa, Odem Shani Source Type: research
14. Providing more answers for patients with supplemental RNA analysis
To help resolve the clinical significance of variants predicted to alter splicing, and identify splice-altering variants in regions outside of the reportable range of our routine hereditary cancer DNA sequencing tests, we initiated an IRB-approved RNA-sequencing research study at Invitae. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - November 1, 2022 Category: Genetics & Stem Cells Authors: Laure Fresard, Keith Nykamp, Nick Kamp-Hughes, John Vincent, Sarah Albritton, Victoria Carlton, Hio Chung Kang, Kate Krempely, Carolina Pardo Source Type: research
15. ClinGen Somatic Cancer expert curation panel for FGFR genes in Genitourinary Cancer
Genomic aberrations disrupting fibroblast growth factor receptors (FGFR) signalling have been implicated in several human cancers and are an emerging focus of targeted therapies. While routine large-scale sequencing has resulted in the identification of numerous variants in the FGFR genes, these variants have never been uniformly and comprehensively classified for their clinical significance has been challenging due to their rarity. Thus, we formed the ClinGen FGFR Somatic Cancer Variant Curation Expert Panel (SC-VCEP) to standardize interpretation of FGFR gene variants, principally in FGFR3, but also FGFR1, FGFR2 and FGFR...
Source: Cancer Genetics and Cytogenetics - November 1, 2022 Category: Genetics & Stem Cells Authors: Ian King, Jason Saliba, Arpad Danos, Ariana Gonzalez, Bethany Baumann, Christine Walko, Erin McMullin, Gokce Toruner, Jeanine Ruggeri, Sayed Ali Hosseini, Kara Bui, Amber Pryzbylski, Sameek Roychowdhury, Shashikant Kulkarni, Obi L. Griffith, Malachi Griff Source Type: research
