Atypical tuberous sclerosis complex presenting as familial renal cell carcinoma with leiomyomatous stroma.
J Pathol Clin Res
; 4(3): 167-174, 2018 07.
Article
en En
| MEDLINE
| ID: mdl-29659200
ABSTRACT
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Esclerosis Tuberosa
/
Angiomiolipoma
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Mutación Missense
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Proteína 2 del Complejo de la Esclerosis Tuberosa
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
Límite:
Humans
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Male
/
Middle aged
Idioma:
En
Revista:
J Pathol Clin Res
Año:
2018
Tipo del documento:
Article
País de afiliación:
Canadá