Atypical tuberous sclerosis complex presenting as familial renal cell carcinoma with leiomyomatous stroma
| Autor: | Maria Daniela D'Agostino, Louis R. Bégin, Nancy Hamel, Simon Tanguay, Somayyeh Fahiminiya, Ismaël Bah, William D. Foulkes |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
congenital hereditary and neonatal diseases and abnormalities Pathology medicine.medical_specialty business.industry urologic and male genital diseases medicine.disease Phenotype female genital diseases and pregnancy complications Germline nervous system diseases Pathology and Forensic Medicine 03 medical and health sciences Tuberous sclerosis 030104 developmental biology 0302 clinical medicine Stroma Renal cell carcinoma 030220 oncology & carcinogenesis medicine Missense mutation TSC2 business Index case |
| Zdroj: | The Journal of Pathology: Clinical Research. 4:167-174 |
| ISSN: | 2056-4538 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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