A shower of second hit events as the cause of multifocal renal cell carcinoma in tuberous sclerosis complex.

Hum Mol Genet
Authors
Keywords
Abstract

Tuberous sclerosis complex (TSC) is a genetic disorder characterized by seizures and tumor formation in multiple organs, mainly in the brain, skin, kidney, lung and heart. Renal cell carcinoma (RCC) occurs in ∼3% of TSC patients, and typically develops at age 1 tumor. The second (male) TSC patient had bilateral partial nephrectomies (both at age 36), with similar findings of multifocal PRCC. NGS analysis of TSC2 in two of these tumors identified a second hit mutation c.2355+1G>T in one sample that was not seen in other tumors. In conclusion, we report the first detailed genetic analysis of RCCs in TSC patients. Molecular studies indicate that tumors developed independently due to various second hit events, suggesting that these patients experienced a 'shower' of second hit mutations in TSC2 during kidney development leading to this severe phenotype.

Year of Publication
2015
Journal
Hum Mol Genet
Volume
24
Issue
7
Pages
1836-42
Date Published
2015 Apr 01
ISSN
1460-2083
URL
DOI
10.1093/hmg/ddu597
PubMed ID
25432535
PubMed Central ID
PMC4355019
Links
Grant list
P01 CA120964 / CA / NCI NIH HHS / United States
1P01CA120964 / CA / NCI NIH HHS / United States
2R37NS031535 / NS / NINDS NIH HHS / United States