Biallelic Alteration and Dysregulation of the Hippo Pathway in Mucinous Tubular and Spindle Cell Carcinoma of the Kidney.
Cancer Discov
; 6(11): 1258-1266, 2016 11.
Article
en En
| MEDLINE
| ID: mdl-27604489
ABSTRACT
Mucinous tubular and spindle cell carcinoma (MTSCC) is a relatively rare subtype of renal cell carcinoma (RCC) with distinctive morphologic and cytogenetic features. Here, we carry out whole-exome and transcriptome sequencing of a multi-institutional cohort of MTSCC (n = 22). We demonstrate the presence of either biallelic loss of Hippo pathway tumor suppressor genes (TSG) and/or evidence of alteration of Hippo pathway genes in 85% of samples. PTPN14 (31%) and NF2 (22%) were the most commonly implicated Hippo pathway genes, whereas other genes such as SAV1 and HIPK2 were also involved in a mutually exclusive fashion. Mutations in the context of recurrent chromosomal losses amounted to biallelic alterations in these TSGs. As a readout of Hippo pathway inactivation, a majority of cases (90%) exhibited increased nuclear YAP1 protein expression. Taken together, nearly all cases of MTSCC exhibit some evidence of Hippo pathway dysregulation. SIGNIFICANCE:
MTSCC is a rare and relatively recently described subtype of RCC. Next-generation sequencing of a multi-institutional MTSCC cohort revealed recurrent chromosomal losses and somatic mutations in the Hippo signaling pathway genes leading to potential YAP1 activation. In virtually all cases of MTSCC, there was evidence of Hippo pathway dysregulation, suggesting a common mechanistic basis for this disease. Cancer Discov; 6(11); 1258-66. ©2016 AACR.This article is highlighted in the In This Issue feature, p. 1197.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Carcinoma de Células Renales
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Biomarcadores de Tumor
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Adenocarcinoma Mucinoso
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Secuenciación de Nucleótidos de Alto Rendimiento
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Transcriptoma
Límite:
Humans
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Middle aged
Idioma:
En
Revista:
Cancer Discov
Año:
2016
Tipo del documento:
Article