Hannah N. Bell, Chandan Kumar-Sinha, R. Mannan, D. Zakalik, Yuping Zhang, R. Mehra, Deepak V Jagtap, S. Dhanasekaran, U. Vaishampayan
{"title":"Pathogenic ATM and BAP1 germline mutations in a case of early-onset, familial sarcomatoid renal cancer","authors":"Hannah N. Bell, Chandan Kumar-Sinha, R. Mannan, D. Zakalik, Yuping Zhang, R. Mehra, Deepak V Jagtap, S. Dhanasekaran, U. Vaishampayan","doi":"10.1101/mcs.a006203","DOIUrl":null,"url":null,"abstract":"Metastatic renal cell carcinoma (RCC) remains an incurable malignancy, despite recent advances in systemic therapies. Genetic syndromes associated with kidney cancer account for only 5%–8% of all diagnosed kidney malignancies, and genetic predispositions to kidney cancer predisposition are still being studied. Genomic testing for kidney cancer is useful for disease molecular subtyping but provides minimal therapeutic information. Understanding how aberrations drive RCC development and how their contextual influences, such as chromosome loss, genome instability, and DNA methylation changes, may alter therapeutic response is of importance. We report the case of a 36-yr-old female with aggressive, metastatic RCC and a significant family history of cancer, including RCC. This patient harbors a novel, pathogenic, germline ATM mutation along with a rare germline variant of unknown significance in the BAP1 gene. In addition, somatic loss of heterozygosity (LOH) in BAP1 and ATM genes, somatic mutation and LOH in the VHL gene, copy losses in Chromosomes 9p and 14, and genome instability are also noted in the tumor, potentially dictating this patient's aggressive clinical course. Further investigation is warranted to evaluate the association of ATM and BAP1 germline mutations with increased risk of RCC and if these mutations should lead to enhanced and early screening.","PeriodicalId":10360,"journal":{"name":"Cold Spring Harbor Molecular Case Studies","volume":null,"pages":null},"PeriodicalIF":1.8000,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"4","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cold Spring Harbor Molecular Case Studies","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1101/mcs.a006203","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 4
Abstract
Metastatic renal cell carcinoma (RCC) remains an incurable malignancy, despite recent advances in systemic therapies. Genetic syndromes associated with kidney cancer account for only 5%–8% of all diagnosed kidney malignancies, and genetic predispositions to kidney cancer predisposition are still being studied. Genomic testing for kidney cancer is useful for disease molecular subtyping but provides minimal therapeutic information. Understanding how aberrations drive RCC development and how their contextual influences, such as chromosome loss, genome instability, and DNA methylation changes, may alter therapeutic response is of importance. We report the case of a 36-yr-old female with aggressive, metastatic RCC and a significant family history of cancer, including RCC. This patient harbors a novel, pathogenic, germline ATM mutation along with a rare germline variant of unknown significance in the BAP1 gene. In addition, somatic loss of heterozygosity (LOH) in BAP1 and ATM genes, somatic mutation and LOH in the VHL gene, copy losses in Chromosomes 9p and 14, and genome instability are also noted in the tumor, potentially dictating this patient's aggressive clinical course. Further investigation is warranted to evaluate the association of ATM and BAP1 germline mutations with increased risk of RCC and if these mutations should lead to enhanced and early screening.
期刊介绍:
Cold Spring Harbor Molecular Case Studies is an open-access, peer-reviewed, international journal in the field of precision medicine. Articles in the journal present genomic and molecular analyses of individuals or cohorts alongside their clinical presentations and phenotypic information. The journal''s purpose is to rapidly share insights into disease development and treatment gained by application of genomics, proteomics, metabolomics, biomarker analysis, and other approaches. The journal covers the fields of cancer, complex diseases, monogenic disorders, neurological conditions, orphan diseases, infectious disease, gene therapy, and pharmacogenomics. It has a rapid peer-review process that is based on technical evaluation of the analyses performed, not the novelty of findings, and offers a swift, clear path to publication. The journal publishes: Research Reports presenting detailed case studies of individuals and small cohorts, Research Articles describing more extensive work using larger cohorts and/or functional analyses, Rapid Communications presenting the discovery of a novel variant and/or novel phenotype associated with a known disease gene, Rapid Cancer Communications presenting the discovery of a novel variant or combination of variants in a cancer type, Variant Discrepancy Resolution describing efforts to resolve differences or update variant interpretations in ClinVar through case-level data sharing, Follow-up Reports linked to previous observations, Plus Review Articles, Editorials, and Position Statements on best practices for research in precision medicine.