Faculty, Staff and Student Publications
Language
English
Publication Date
1-1-2024
Journal
Journal of Investigative Medicine High Impact Case Reports
DOI
10.1177/23247096241286370
PMID
39369320
PMCID
PMC11457202
PubMedCentral® Posted Date
10-6-2024
PubMedCentral® Full Text Version
Post-print
Abstract
While renal cell carcinoma (RCC) is often linked to smoking, obesity, and hypertension, hereditary forms also account for about 3% of RCC cases. Notably, NCCN guidelines identify 7 major hereditary syndromes associated with an increased RCC risk. Inherited mutations in DNA repair genes, such as ATM, BRCA, and TP53, significantly increase the risk of various cancers. Biallelic pathogenic mutations in ATM cause Ataxia-Telangiectasia (A-T) syndrome, while heterozygous germline pathogenic ATM mutations, present in about 1% of the population, also elevate cancer risk. RCC has not traditionally been associated with germline pathogenic ATM mutations, only limited retrospective analyses have identified such mutations. This case report presents a 68-year-old woman with a germline pathogenic ATM mutation (c.8786+1 G>A) who developed high-risk clear cell RCC followed by an acquired somatic VHL mutation in RCC and a 3-cm serous cystadenoma, illustrating the double-hit phenomenon. Her brother, who shares the same germline pathogenic mutation, was diagnosed with pancreatic cancer and prostate cancer. This case highlights the potential use for enhanced screening protocols for RCC in patients who have germline pathogenic ATM mutations and the importance of research in targeted treatments for tumors driven by dual genetic mechanisms. Increased awareness and vigilant screening for RCC are crucial in managing hereditary cancer syndromes effectively.
Keywords
Humans, Carcinoma, Renal Cell, Ataxia Telangiectasia Mutated Proteins, Female, Germ-Line Mutation, Aged, Kidney Neoplasms, Von Hippel-Lindau Tumor Suppressor Protein, Male, Genetic Predisposition to Disease, ATM, VHL, clear-cell renal cell carcinoma, germline mutation, somatic mutation
Published Open-Access
yes
Recommended Citation
Chan, Kok Hoe; Clavijo, Nicolas Duque; Ayala, Gustavo; et al., "Double Hit in Clear-Cell Renal Cell Carcinoma With Germline Pathogenic ATM Mutation and Somatic VHL Mutation" (2024). Faculty, Staff and Student Publications. 3553.
https://digitalcommons.library.tmc.edu/uthmed_docs/3553