High throughput molecular profiling reveals differential mutation patterns in intrahepatic cholangiocarcinomas arising in chronic advanced liver diseases.
Mod Pathol
; 27(5): 731-9, 2014 May.
Article
em En
| MEDLINE
| ID: mdl-24186137
ABSTRACT
Intrahepatic cholangiocarcinomas occur mostly in the normal liver but they also arise in chronic advanced liver diseases. However, genetic differences between two groups have yet to be examined. High throughput mass spectrometry-based platform was used to interrogate mutations in intrahepatic cholangiocarcinomas and to compare the mutation profiles between 43 intrahepatic cholangiocarcinomas with normal liver and 38 with chronic advanced liver diseases. Forty seven mutations in 11 genes were identified in 38 of 81 cases (46.9%). The most commonly mutated gene was KRAS (11/81, 13.6%), followed by MLH1 (7/81, 8.6%), NRAS (7/81, 8.6%), GNAS (6/81, 7.4%), and EGFR (6/81, 7.4%). BRAF, APC, PIK3CA, CDKN2A, PTEN, and TP53 mutations were found with less than 5%. Overall mutation rate of intrahepatic cholangiocarcinomas with chronic advanced liver disease (15/38, 39.5%, 95% confidence interval 23.9-55.0) was lower than that of intrahepatic cholangiocarcinomas with normal liver (23/43, 53.5%, 95% confidence interval 38.5-68.3). Intrahepatic cholangiocarcinomas with chronic advanced liver disease showed higher EGFR mutation rate (5/38, 13.2% vs 1/43, 2.3%) and lower mutation rates of KRAS (3/38, 7.9% vs 8/43, 18.6%), MLH1 (2/38, 5.3% vs 5/43, 11.6%), and GNAS (1/38, 2.6% vs 5/43, 11.6%), compared with those in intrahepatic cholangiocarcinomas with normal liver. Mutations in PIK3CA, PTEN, CDKN2A, and TP53 were harbored only in intrahepatic cholangiocarcinomas with normal liver. KRAS (P=0.0075) or GNAS mutations (P=0.0256) were associated with poor overall survival in all patients with intrahepatic cholangiocarcinoma. Differential mutation patterns of intrahepatic cholangiocarcinomas with chronic advanced liver disease suggest different cholangiocarcinogenesis depending upon the predisposing factors, and support that different strategy for targeted therapy should be applied in intrahepatic cholangiocarcinoma subtypes.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias dos Ductos Biliares
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Colangiocarcinoma
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Hepatopatias
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Mutação
Tipo de estudo:
Prognostic_studies
Limite:
Adult
/
Aged
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Female
/
Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Mod Pathol
Assunto da revista:
PATOLOGIA
Ano de publicação:
2014
Tipo de documento:
Article