Journal
JOURNAL OF PATHOLOGY CLINICAL RESEARCH
Volume 4, Issue 3, Pages 167-174Publisher
WILEY
DOI: 10.1002/cjp2.104
Keywords
tuberous sclerosis complex; renal cell carcinoma; TSC2; renal cell carcinoma with (angio)leiomyomatous stroma; renal angiomyoadenomatous tumour
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Funding
- Canadian Institutes of Health Research [FDN-148390]
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We report an atypical tuberous sclerosis complex (TSC) phenotype presenting as familial multiple renal cell carcinomas (RCCs) with (angio)leiomyomatous stroma (RCCLS) (5/7 familial RCCs) on a background of multiple angiomyolipomas, hypopigmented skin macules, and absence of neurological anomalies. In the index case and three relatives, germline genetic testing identified a heterozygous TSC2 missense pathogenic variant [c.2714 G>A, (p.Arg905Gln)], a rare TSC-associated alteration which has previously been associated with a milder TSC phenotype. Whole-exome sequencing of five RCCs from the index case and one RCC from his mother demonstrated either unique tumour-specific deleterious second hits in TSC2 or significant allelic imbalance at the TSC2 gene locus (5/6 RCCs). This study confirms the key tumourigenic role of tumour-specific TSC2 second hits in TSC-associated RCCs and supports the notion that RCCLS may be strongly related to abnormalities of the mTOR pathway.
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