Cancer Genetics最新文献_第5页

2. Diagnostic next generation sequencing to detect MYD88 L265P in lymphoplasmacytic lymphoma compared to ddPCR 2.诊断性新一代测序检测淋巴浆细胞性淋巴瘤中的 MYD88 L265P 与 ddPCR 的比较

IF 1.4 4区医学

Cancer Genetics Pub Date : 2024-08-01 DOI: 10.1016/j.cancergen.2024.08.004

Lauren M. Wainman , Guohong Huang , Donald C. Green , Eric Y. Loo , Prabhjot Kaur , Parth Shah , Jeremiah Karrs

{"title":"2. Diagnostic next generation sequencing to detect MYD88 L265P in lymphoplasmacytic lymphoma compared to ddPCR","authors":"Lauren M. Wainman , Guohong Huang , Donald C. Green , Eric Y. Loo , Prabhjot Kaur , Parth Shah , Jeremiah Karrs","doi":"10.1016/j.cancergen.2024.08.004","DOIUrl":"10.1016/j.cancergen.2024.08.004","url":null,"abstract":"<div><div>Lymphoplasmacytic lymphoma (LPL) is a B-cell lymphoproliferative disorder characterized by bone marrow infiltration of lymphoplasmacytic cells. Studies have identified <em>MYD88</em> L265P mutation as a diagnostic marker to distinguish LPL from other small B-cell lymphomas (e.g. marginal zone lymphoma, chronic lymphocytic leukemia). However, detection rates for this mutation have varied depending on the analytic methodology, with data suggesting that routine Next Generation Sequencing (NGS) does not demonstrate the required sensitivity to reliably detect <em>MYD88</em> L265P. NGS has become a work-horse of the modern genetic laboratory by basketing multiple single-gene assays into one multiplexed assay. In several routine cases, visual observation using IGV demonstrated <em>MYD88</em> L265P variants in cases of suspected LPL with low tumor content. To study this, we performed droplet digital PCR (ddPCR) and our routine NGS for <em>MYD88</em> L265P in a cohort of 35 cases of lymphoid neoplasms (25 LPL, 6 CLL, 4 negative bone marrow cases). Our standard NGS method achieved an average depth of ∼535 reads across this region. We utilized manual review and BAMtools to assess <em>MYD88</em> L265P in NGS cases. Limit of detection for ddPCR was determined to be 0.3% variant allele frequency (VAF) with 10ng DNA input. <em>MYD88</em> L265P VAF detection by NGS and ddPCR was comparable down to 0.5% VAF (R<sup>2</sup>=0.968). Setting an appropriate threshold for detection based on ddPCR results resulted in zero NGS false positives. This study demonstrates that NGS can be a sensitive and reliable method for detection of <em>MYD88</em> L265P with adequate coverage and specific assessment parameters.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"286 ","pages":"Page S1"},"PeriodicalIF":1.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142322862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

59. What the TERT? - A telomerase reverse transcriptase case study 59.什么是 TERT？- 端粒酶逆转录酶案例研究

IF 1.4 4区医学

Cancer Genetics Pub Date : 2024-08-01 DOI: 10.1016/j.cancergen.2024.08.061

Yeshmira Moodley, Longqian Yang, Bronwyn Neumann, Amanda Dixon-McIver

{"title":"59. What the TERT? - A telomerase reverse transcriptase case study","authors":"Yeshmira Moodley, Longqian Yang, Bronwyn Neumann, Amanda Dixon-McIver","doi":"10.1016/j.cancergen.2024.08.061","DOIUrl":"10.1016/j.cancergen.2024.08.061","url":null,"abstract":"<div><div>Telomerase reverse transcriptase is a catalytic subunit of the telomerase protein that is involved in the maintenance of genomic stability. <em>TERT</em> aberrations are important biomarkers in the diagnosis, prognosis, and treatment of many human cancers. The <em>TERT</em> promoter has proven to be a difficult region of testing amongst a variety of currently available technologies.</div><div><em>TERT</em> promoter mutation analysis was performed on brain tissue of a 62-year old male meningioma patient using MALDI-TOF (Agena Bioscience MassARRAY platform) and detected a low frequency <em>TERT</em> mutation. The pathologist questioned the result and sent some of the sample for additional testing to 2 different referral laboratories - one aliquot was sent for Pyrosequencing and the other for NGS - both with a higher limit of detection than MALDI-TOF. Neither methodology detected a <em>TERT</em> mutation. On the basis of these result the diagnosis was changed.</div><div>Certain of our <em>TERT</em> mutation, an aliquot of the remaining extracted DNA was sent for digital droplet PCR (ddPCR) which has the same limit of detection as our MALDI-TOF platform. A <em>TERT</em> mutation was confirmed.</div><div>This case highlights the challenges in <em>TERT</em> promoter mutation analysis as well as the significance of confirmatory testing. The importance of confirming results using platforms with an appropriate limit of detection is paramount in reducing under-reporting of low level mutations of clinical significance.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"286 ","pages":"Page S19"},"PeriodicalIF":1.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142323472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

66. Prognostic impact of genomic testing results in patients undergoing transplantation for myelofibrosis 66.基因组检测结果对骨髓纤维化移植患者预后的影响

IF 1.4 4区医学

Cancer Genetics Pub Date : 2024-08-01 DOI: 10.1016/j.cancergen.2024.08.068

Xiaoyu Qu , Emily Stevens , Matt Fitzgibbon , Lan Beppu , Tim M. Monahan , Cecilia C.S. Yeung , Derek L. Stirewalt , David Wu , Jerald Radich , H. Joachim Deeg , Min Fang

{"title":"66. Prognostic impact of genomic testing results in patients undergoing transplantation for myelofibrosis","authors":"Xiaoyu Qu , Emily Stevens , Matt Fitzgibbon , Lan Beppu , Tim M. Monahan , Cecilia C.S. Yeung , Derek L. Stirewalt , David Wu , Jerald Radich , H. Joachim Deeg , Min Fang","doi":"10.1016/j.cancergen.2024.08.068","DOIUrl":"10.1016/j.cancergen.2024.08.068","url":null,"abstract":"<div><div>Despite its known superior detection rate for chromosomal anomalies compared to karyotype and FISH studies, Chromosome Genomic Array Testing (CGAT) is not used as a routine clinical test for myelofibrosis. We investigated the prognostic significance of CGAT and mutation results by NGS in myelofibrosis patients who underwent hematopoietic cell transplantation between 2000 and 2017 at our center (n=44). CGAT was done in a CLIA lab using CytoScanHD (ThermoFisher). NGS was performed either in a CLIA lab using UW Heme Gene Panel by NGS (n=9) or retrospectively at a research lab using TruSight myeloid panel (Illumina, n=35). Twenty-four patients (55%) had abnormal CGAT results. In 18 patients (41%), CGAT uniquely demonstrated cnLOH, with 9p cnLOH being the most frequent (n=8, 18%). Thirty-five patients had myeloproliferative neoplasm (MPN) driver mutations: 17 (39%) <em>JAK2</em> pV617F, 16 (36%) <em>CALR</em> exon 9 mutation, and two <em>MPL</em> pW515 (5%). With a median of 91 (range 2-258) months of follow-up, event-free survival (EFS; event referring to relapse) was 59%, and overall survival (OS) was 68%. Abnormal CGAT results (n=24, P=0.03), <em>U2AF1</em> mutation (n=5, P=0.028) and 1q gain (n=3, P=0.009) were associated with worse EFS. The genetic aberrations had no significant effect on OS in this cohort. <em>ASXL1</em> mutations (n=14) appeared to associate with a later onset of chronic graft-versus-host-disease (P=0.03). In conclusion, assessments by both CGAT and NGS pre-transplantation provide valuable outcome information and may be considered as routine clinical testing for myelofibrosis</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"286 ","pages":"Page S21"},"PeriodicalIF":1.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142323397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

34. Identifying challenges in variant normalization 34.确定变体规范化的挑战

IF 1.4 4区医学

Cancer Genetics Pub Date : 2024-08-01 DOI: 10.1016/j.cancergen.2024.08.036

Anastasia Bratulin , Wesley A. Goar , Kori Kuzma , Lawrence Babb , Kyle Ferriter , Terry O'Neill , Austin A. Antoniou , Jeremy A. Arbesfeld , Daniel Puthawala , James S. Stevenson , Jiachen Liu , Xuelu Liu , Brian Walsh , William C. Ray , Savanna Funk , Bimal P. Chaudhari , Heidi L. Rehm

{"title":"34. Identifying challenges in variant normalization","authors":"Anastasia Bratulin , Wesley A. Goar , Kori Kuzma , Lawrence Babb , Kyle Ferriter , Terry O'Neill , Austin A. Antoniou , Jeremy A. Arbesfeld , Daniel Puthawala , James S. Stevenson , Jiachen Liu , Xuelu Liu , Brian Walsh , William C. Ray , Savanna Funk , Bimal P. Chaudhari , Heidi L. Rehm","doi":"10.1016/j.cancergen.2024.08.036","DOIUrl":"10.1016/j.cancergen.2024.08.036","url":null,"abstract":"<div><div>Genomic medicine relies on collecting information from multiple sources to make optimal therapeutic and diagnostic decisions for the patient. However, integration of this information, at the time of variant interpretation, is a major bottleneck. Challenges including inconsistent formats (e.g. HGVS and SPDI), and variant contexts (genome and proteome), increase the time and effort required to formulate and communicate a complete variant interpretation. To more clearly understand inter-resource differences in variant representation, variants from the Clinical Interpretations of Variants in Cancer (CIViC), Molecular Oncology Almanac (MOAlmanac), and ClinVar were evaluated using a normalization protocol. Of the variants in the knowledgebases, ∼53% of the CIViC, ∼42% of the MOAlmanac, and ∼99% of ClinVar variants were successfully normalized. We categorically assessed remaining variants for which normalization methods are still needed, and analyzed these for clinical impact. Gene fusion (e.g. 'ALK G1202R') and region-defined variant categories (e.g. '3′ UTR Mutations') respectively constitute 16% and 10% of all the variants that were not normalized, and were found to hold the greatest potential clinical impact. Additionally, fusion variants are responsible for ∼25% of all of the evidence items associated with not normalized variants from CIViC and MOAlmanac, illustrating the weight that fusion variants carry in the overall group. The Variation Normalizer is an open-source toolkit and is available for use with independent data sets to facilitate precise matching of evidence from knowledgebases to genomic variant data.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"286 ","pages":"Page S11"},"PeriodicalIF":1.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142323288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

43. Challenges of classifying variants associated with disorders of somatic mosaicism and guideline creation 43.体细胞嵌合紊乱相关变异的分类挑战与准则制定

IF 1.4 4区医学

Cancer Genetics Pub Date : 2024-08-01 DOI: 10.1016/j.cancergen.2024.08.045

Alexa Dickson, Kevin Bowling, Fernando Zazueta, Yang Cao

{"title":"43. Challenges of classifying variants associated with disorders of somatic mosaicism and guideline creation","authors":"Alexa Dickson, Kevin Bowling, Fernando Zazueta, Yang Cao","doi":"10.1016/j.cancergen.2024.08.045","DOIUrl":"10.1016/j.cancergen.2024.08.045","url":null,"abstract":"<div><div>Disorders of somatic mosaicism (DoSM) constitute rare genetic disorders characterized by post-zygotic events leading to segmental distribution of disease. The early presentation of associated phenotypes often mimics germline diseases, complicating molecular diagnosis. Additionally, current guidelines from the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) focus specifically on germline and cancer variants, complicating the interpretation of DoSM-associated somatic variation. The ClinGen Brain Malformation Expert Panel guidelines have created valuable updates to account for brain-specific disorders of somatic mosaicism, but their applicability to the diverse DoSM presentations is limited. At Washington University School of Medicine, we have identified shortcomings in applying ACMG/AMP germline guidelines to DoSM variants, prompting the development of DoSM-specific variant interpretation guidelines. Leveraging our laboratory's extensive experience in somatic variation interpretation, we have developed DoSM guidelines that are applicable across genes and clinical contexts pertinent to non-cancerous somatic testing. These guidelines address the critical need for accurate somatic variant interpretation in DoSM, where treatment advances hinge on understanding the overlap between somatic variants in DoSM and tumors. This comprehensive framework addresses the gap in existing guidelines, offering an iinvaluable resource for clinical laboratories engaged in non-cancerous somatic testing and advancing precision medicine for patients with DoSM. We will present the developed guidelines, discuss challenges specific to DoSM and criteria development, and interesting cases studies where DoSM-specific guidelines were critical to accurate diagnosis.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"286 ","pages":"Page S14"},"PeriodicalIF":1.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142323297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

62. Characterization of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) with KMT2A amplification 62.骨髓增生异常综合征（MDS）和急性髓性白血病（AML）KMT2A 扩增的特征描述

IF 1.4 4区医学

Cancer Genetics Pub Date : 2024-08-01 DOI: 10.1016/j.cancergen.2024.08.064

John O'Shea, Jian Zhao, Erica Andersen, Bo Hong

{"title":"62. Characterization of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) with KMT2A amplification","authors":"John O'Shea, Jian Zhao, Erica Andersen, Bo Hong","doi":"10.1016/j.cancergen.2024.08.064","DOIUrl":"10.1016/j.cancergen.2024.08.064","url":null,"abstract":"<div><div><em>KMT2A</em> amplification is a rare high risk cytogenetic abnormality in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), which has been associated with complex karyotype, resistance to chemotherapy and higher frequency in elderly patients. Comprehensive elucidation of cytogenetic signatures in AML/MDS with <em>KMT2A</em> amplification, the subsequent clinical impact, as well as accompanying gene mutation profile would be beneficial for stratified patient care.</div><div>Herein, we present karyotyping/fluorescence in situ hybridization (FISH) data on 42 AML/MDS patients with <em>KMT2A</em> amplification, along with next generation sequencing (NGS) results and prognostic information in a subset of patients. The median age at diagnosis was 70 years. The male to female ratio was 1.8 (27:15). The median survival was 45 days. <em>KMT2A</em> amplification was identified by FISH. Chromosome analysis showed complex karyotype in all cases analyzed (n=38). The structural mechanisms associated with <em>KMT2A</em> amplification included homogeneously staining region (n=27), double minutes (n=6) and ring chromosome 11 (n=8). Deletions of 5q (64%) and 17p (62%) were the most common concurrent cytogenetic findings. Additional major concurrent cytogenetic abnormalities included loss of 7q (31%) and gain of chromosome 8 (29%). NGS results were available for 14 cases and <em>TP53</em> mutation was the most common alteration (n=12). Other mutations were detected in <em>TET2</em> (n=2), <em>NSD1</em> (n=2), <em>SAMD9L</em> (n=2), <em>DNMT3A</em> (n=1), <em>U2AF2</em> (n=1), <em>FLT3</em> (TKD, n=1), <em>NOTCH1</em> (n=1) and <em>SMC3</em> (n=1).</div><div>AML/MDS with <em>KMT2A</em> amplification is associated with poor outcome and specific concurrent cytogenetic and molecular abnormalities. Documenting additional data is valuable for improving the treatment landscape in these myeloid neoplasms.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"286 ","pages":"Page S20"},"PeriodicalIF":1.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142323478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

39. Modifying cancer variant interpretation guidelines for the curation of histone H3 variants: The 'next step' of the Cl 39.修改癌症变异体解释指南，用于组蛋白 H3 变异体的整理：组蛋白 H3 变异的 "下一步

IF 1.4 4区医学

Cancer Genetics Pub Date : 2024-08-01 DOI: 10.1016/j.cancergen.2024.08.041

Laveniya Satgunaseelan , Somak Roy , Shivani Golem , Jianling Ji , Yassmine Akkari , Elizabeth Spiteri , Arpad Danos , Wan-Hsin Lin , Cameron Grisdale , Obi Griffith , Malachi Griffith , Jason Saliba , David Meredith

{"title":"39. Modifying cancer variant interpretation guidelines for the curation of histone H3 variants: The 'next step' of the Cl","authors":"Laveniya Satgunaseelan , Somak Roy , Shivani Golem , Jianling Ji , Yassmine Akkari , Elizabeth Spiteri , Arpad Danos , Wan-Hsin Lin , Cameron Grisdale , Obi Griffith , Malachi Griffith , Jason Saliba , David Meredith","doi":"10.1016/j.cancergen.2024.08.041","DOIUrl":"10.1016/j.cancergen.2024.08.041","url":null,"abstract":"<div><div>Histone H3 variants pose numerous challenges for curation due to varied nomenclature for their isoforms and encoding genes. These are further compounded by the tumor-specific settings in which histone H3 variants occur. Therefore, the Histone H3 SC-VCEP aimed to adapt and modify the ClinGen/CGC/VICC Oncogenicity SOP and AMP/ASCO/CAP guidelines for the interpretation of H3 variants specific to diffuse midline glioma, H3 K27-altered and diffuse hemispheric glioma, H3 G34-mutant.</div><div>The main proposed specifications to the ClinGen/CGC/VICC Oncogenicity SOP include: (1) the incorporation of trimethylation loss at the K27 residue and functional studies at G34 into evidence code OS2 and (2) stipulation of location at a 'conserved residue affecting epigenetic modification (e.g. histone H3 K27, G34, or K36)' for evidence code OM1.</div><div>The main proposed modifications to the ClinGen/CGC/VICC Oncogenicity SOP include: (1) an 'OS1_moderate' criterion (2 points), allowing for the same amino acid change as a previously established oncogenic variant in a homologous H3 gene; (2) an 'OS2_supportive' criterion (1 point), incorporating supportive evidence of frequent co-occurring variants (e.g. TP53, PDGFRA, ACVR1) or other supportive evidence of histone H3 mutation (e.g. gene expression analysis); and (3) an alternate OP2 criterion (1 point) applied when clinicopathologic features align with a corresponding histone mutant glioma in the WHO Classification. This novel modification introduces clinicopathological correlation into the assessment of oncogenicity. Evidence specifications have also been made to the AMP/ASCO/CAP guidelines.</div><div>Evaluation of our proposed changes to the guidelines is underway in a defined set of pilot variants.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"286 ","pages":"Pages S12-S13"},"PeriodicalIF":1.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142323293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

41. Step 2 updates for the oncogenic assessment of FLT3 variants by the ClinGen FLT3 somatic cancer variant curation expert 41.ClinGen FLT3 体癌基因变异整理专家对 FLT3 变异致癌评估的第二步更新

IF 1.4 4区医学

Cancer Genetics Pub Date : 2024-08-01 DOI: 10.1016/j.cancergen.2024.08.043

Nathan Kopp , Mani Coumarane , Rong He , Yuwen Li , Somayyeh Fahiminiya , Nikita Mehta , Shivani Golem , Xiaonan Zhao , Yiming Zhong , Haluk Kavus , Xiangqiang Shao , Rashmi Kanagal-Shamanna , Jason Saliba , Obi Griffith , Malachi Griffith , Xinjie Xu , Kilannin Krysiak , Arpad Danos

{"title":"41. Step 2 updates for the oncogenic assessment of FLT3 variants by the ClinGen FLT3 somatic cancer variant curation expert","authors":"Nathan Kopp , Mani Coumarane , Rong He , Yuwen Li , Somayyeh Fahiminiya , Nikita Mehta , Shivani Golem , Xiaonan Zhao , Yiming Zhong , Haluk Kavus , Xiangqiang Shao , Rashmi Kanagal-Shamanna , Jason Saliba , Obi Griffith , Malachi Griffith , Xinjie Xu , Kilannin Krysiak , Arpad Danos","doi":"10.1016/j.cancergen.2024.08.043","DOIUrl":"10.1016/j.cancergen.2024.08.043","url":null,"abstract":"<div><div>Variant interpretation guidelines aid genetic professionals in assessing the strength of evidence for the variant pathogenicity and clinical significance. Currently, there are no standard guidelines for evaluation of <em>FLT3</em> variants, leading to variability in interpretation of <em>FLT3</em> tyrosine kinase and non-tyrosine kinase variants. The FLT3 Somatic Cancer Variant Curation Expert Panel (SC-VCEP), within the ClinGen Somatic Cancer CDWG, is actively developing the variant oncogenicity interpretation rules for the <em>FLT3</em> gene using ClinGen/CGC/VICC (PMID: <span><span>35101336</span><svg><path></path></svg></span>) to facilitate accurate classification of <em>FLT3</em> variants.</div><div>We will provide an update on the <em>FLT3</em>-specific modifications to evidence criteria OP1/SBP1 and OP4/SBS1. To address OP1/SBP1 we assessed multiple <em>in silico</em> prediction tools and their performance on FLT3-specific variants. Based on the analysis, we selected ClinPred and REVEL as optimal prediction tools for further evaluation during the pilot phase. We also modify the population allele frequency criteria for OP4/SBS1 using the spectrum of allele frequency of <em>FLT3</em> variants. Recognizing the need for applicability to internal tandem duplication (ITD) variants, the strength of OM2 has been increased to OM2_strong for this variant type. With these updates, all rules have been evaluated and modifications/specifications proposed for OVS1, OS2/SBS2, OS3/OM3/OP3, OM1, OM2, OP1/SBP1, OP2, SBVS1, and OP4/SBS1. Once approved, the validity of the rules will be assessed on a set of pilot variants.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"286 ","pages":"Page S13"},"PeriodicalIF":1.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142323295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

52. A ClinGen Somatic curation effort focused on EGFR variants 52.ClinGen 体系整理工作侧重于表皮生长因子受体变异

IF 1.4 4区医学

Cancer Genetics Pub Date : 2024-08-01 DOI: 10.1016/j.cancergen.2024.08.054

Arpad Danos , Jason Saliba , Laura Corson , Daniel Jay Brat , Destiney Allen , Gokce Toruner , Haleh Farzanmehr , Haluk Kavus , Ian King , Ariana Gonzalez , Lauren Akesson , Liz Spiteri , Mamta Rao , Rimas Lukas , Shivani Golem , Obi Griffith , Malachi Griffith , Madina Sukhanova , Laveniya Satgunaseelan

{"title":"52. A ClinGen Somatic curation effort focused on EGFR variants","authors":"Arpad Danos , Jason Saliba , Laura Corson , Daniel Jay Brat , Destiney Allen , Gokce Toruner , Haleh Farzanmehr , Haluk Kavus , Ian King , Ariana Gonzalez , Lauren Akesson , Liz Spiteri , Mamta Rao , Rimas Lukas , Shivani Golem , Obi Griffith , Malachi Griffith , Madina Sukhanova , Laveniya Satgunaseelan","doi":"10.1016/j.cancergen.2024.08.054","DOIUrl":"10.1016/j.cancergen.2024.08.054","url":null,"abstract":"<div><div>As next generation sequencing becomes a routine part of clinical diagnostic and follow up workup for tumor assessment, consensus on cancer variant interpretation and expanded knowledgebase curation is needed. <em>EGFR</em> (Epidermal Growth Factor Receptor) is a well recognized oncogene and <em>EGFR</em> SNVs, CNVs, indels, and fusions have important predictive, diagnostic, and prognostic roles in a variety of cancer types. A definitive collection of tumor-specific <em>EGFR</em> somatic variants and their responses to FDA-approved EGFR inhibitors has not yet been assembled and <em>EGFR</em>-specific guidelines for defining variant oncogenicity have not been proposed. Due to their growing clinical relevance, the ClinGen Somatic Clinical Domain Working Group Solid Tumor Taskforce (STTf) performed a pilot curation effort on 15 <em>EGFR</em> fusions, and a number of curation challenges were noted. For instance, <em>EGFR</em> fusions can be primary events in cancer or part of complex molecular alterations (e.g., involving amplification). The group will compile a list of EGFR fusions and collect data on characteristics such as genomic breakpoints, tumor-type associations, functional evidence, and sensitivity to inhibitors. We are forming an <em>EGFR</em> Somatic Cancer Variant Curation Expert Panel (<em>EGFR</em> SC-VCEP) to develop oncogenicity classification recommendations specific to <em>EGFR</em> fusions with future expansion to other <em>EGFR</em> sequence changes. The Step 1 ClinGen SC-VCEP application is in-progress for this effort. The results of this expert-led curation and the resulting guidelines will be publicly available through multiple avenues including the CIViC knowledgebase and ClinVar.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"286 ","pages":"Page S17"},"PeriodicalIF":1.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142322860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

71. Validation of automated cell counter instruments for downstream cytogenetic testing 71.用于下游细胞遗传学检测的自动细胞计数器的验证

IF 1.4 4区医学

Cancer Genetics Pub Date : 2024-08-01 DOI: 10.1016/j.cancergen.2024.08.073

Derek Smith, Wenhua Zhou, Eric Fredrickson, Erica Andersen, Jian Zhao

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引用次数: 0