Pathogenic ATM and BAP1 germline mutations in a case of early-onset, familial sarcomatoid renal cancer.
Cold Spring Harb Mol Case Stud
; 8(3)2022 04.
Article
in En
| MEDLINE
| ID: mdl-35483881
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Sarcoma
/
Soft Tissue Neoplasms
/
Carcinoma, Renal Cell
/
Kidney Neoplasms
Type of study:
Diagnostic_studies
Limits:
Adult
/
Female
/
Humans
Language:
En
Journal:
Cold Spring Harb Mol Case Stud
Year:
2022
Document type:
Article
Affiliation country:
United States