Pathogenic ATM and BAP1 germline mutations in a case of early-onset, familial sarcomatoid renal cancer

IF 1.8 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Cold Spring Harbor Molecular Case Studies Pub Date : 2022-04-01 DOI:10.1101/mcs.a006203
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.
查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
早发性家族性肉瘤样肾癌的病原性ATM和BAP1种系突变1例
转移性肾细胞癌(RCC)仍然是一种无法治愈的恶性肿瘤,尽管最近在全身治疗方面取得了进展。与肾癌相关的遗传综合征仅占所有诊断出的肾脏恶性肿瘤的5%-8%,肾癌易感性的遗传易感性仍在研究中。肾癌的基因组检测对疾病分子分型有用,但提供的治疗信息很少。了解畸变如何驱动RCC的发展,以及它们的背景影响,如染色体丢失、基因组不稳定和DNA甲基化变化,如何改变治疗反应是很重要的。我们报告一例36岁的女性与侵袭性,转移性肾细胞癌和显著的癌症家族史,包括肾细胞癌。该患者携带一种新的、致病性的种系ATM突变,以及BAP1基因中一种罕见的、意义未知的种系变异。此外,BAP1和ATM基因的体细胞杂合性缺失(LOH)、VHL基因的体细胞突变和LOH、染色体9p和14的拷贝丢失以及基因组不稳定也在肿瘤中被注意到,这可能决定了该患者的侵袭性临床病程。需要进一步的研究来评估ATM和BAP1种系突变与RCC风险增加的关系,以及这些突变是否应该导致加强和早期筛查。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
Cold Spring Harbor Molecular Case Studies
Cold Spring Harbor Molecular Case Studies MEDICINE, RESEARCH & EXPERIMENTAL-
CiteScore
3.20
自引率
0.00%
发文量
54
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.
期刊最新文献
Rapid genome diagnosis of alveolar capillary dysplasia leading to treatment in a child with respiratory and cardiac failure. Reclassification of the HPGD p.Ala13Glu variant causing primary hypertrophic osteoarthropathy. The importance of escalating molecular diagnostics in patients with low-grade pediatric brain cancer. Novel pathogenic PDX1 gene variant in a Korean family with maturity-onset diabetes of the young. Novel pathogenic UQCRC2 variants in a female with normal neurodevelopment.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1