Frequent mutations of KRAS in addition to BRAF in colorectal serrated adenocarcinoma
| Autor: | Stefanius, Karoliina, Ylitalo, Laura, Tuomisto, Anne, Kuivila, Rami, Kantola, Tiina, Sirniö, Päivi, Karttunen, Tuomo J, Mäkinen, Markus J |
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| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Adult
Male Proto-Oncogene Proteins B-raf congenital hereditary and neonatal diseases and abnormalities endocrine system diseases serrated adenocarcinoma colorectal cancer DNA hypermethylation Adenocarcinoma hMLH1 BRAF Proto-Oncogene Proteins p21(ras) Proto-Oncogene Proteins KRAS Humans neoplasms Aged Aged 80 and over Original Articles Middle Aged digestive system diseases Mutation ras Proteins Female Microsatellite Instability MGMT Colorectal Neoplasms |
| Zdroj: | Histopathology |
| ISSN: | 1365-2559 0309-0167 |
| Popis: | Aims To define the occurrence of KRAS and BRAF mutations, microsatellite instability (MSI), and MGMT and hMLH1 methylation and expression in colorectal serrated adenocarcinoma. Methods and results KRAS codon 12/13 and 59/61 and BRAF V600E mutations, MSI, and MGMT and hMLH1 methylation and expression in 42 serrated adenocarcinomas and 17 serrated adenomas were compared with those in 59 non-serrated colorectal carcinomas (CRCs) and nine adenomas. KRAS and BRAF mutations were observed in 45% and 33% of serrated adenocarcinomas and in 27% and 0% of non-serrated CRCs (P < 0.001). The KRAS c12G→A transition was the predominant type of mutation in serrated adenocarcinomas. Forty-two per cent of BRAF-mutated serrated adenocarcinomas showed high-level MSI (MSI-H) (P = 0.075), 100% showed hMLH1 methylation (P = 0.001) and 90.9% showed MGMT methylation (P = 0.019). Fifty-six per cent of serrated adenocarcinomas with microsatellite stability/low-level microsatellite instability harboured KRAS mutations. In non-serrated cancers, KRAS mutations were not associated with MSI status. Conclusions A high combined mutation rate (79–82%) of KRAS and BRAF in serrated adenomas and adenocarcinomas indicates that mitogen-activated protein kinase activation is a crucial part of the serrated pathway. BRAF mutations are specific for serrated adenocarcinoma and identify a subset of serrated adenocarcinomas with gene methylation and a tendency for MSI-H. A high frequency of KRAS mutations in serrated adenocarcinomas suggests that a significant proportion of KRAS-mutated CRCs originate from serrated precursors, thus challenging the traditional model of Vogelstein. |
| Databáze: | OpenAIRE |
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