BRAF mutation, CpG island methylator phenotype and microsatellite instability occur more frequently and concordantly in mucinous than non‐mucinous colorectal cancer

Mucinous colorectal cancer (CRC) has been reported to have distinct clinicopathological and genetic characteristics. However, the incidence and the relationship among microsatellite instability (MSI), CpG island methylator phenotype (CIMP) and BRAF and KRAS mutations in mucinous and non‐mucinous CRC...

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Bibliographic Details
Published in:International journal of cancer 2006-06, Vol.118 (11), p.2765-2771
Main Authors: Tanaka, Hirofumi, Deng, Guoren, Matsuzaki, Koji, Kakar, Sanjay, Kim, Grace E., Miura, Soichiro, Sleisenger, Marvin H., Kim, Young S.
Format: Article
Language:English
Subjects:
Adenocarcinoma, Mucinous - genetics
Adenocarcinoma, Mucinous - pathology
Aged
Aged, 80 and over
Biological and medical sciences
BRAF mutation
Colonic Neoplasms - genetics
Colonic Neoplasms - pathology
CpG island methylator phenotype
CpG Islands - genetics
DNA Methylation
DNA Mutational Analysis
Epigenesis, Genetic
Female
Gastroenterology. Liver. Pancreas. Abdomen
Genomic Instability
Humans
KRAS mutation
Male
Medical sciences
microsatellite instability
Microsatellite Repeats
Middle Aged
mucinous colorectal cancer
Phenotype
Proto-Oncogene Proteins B-raf - genetics
Stomach. Duodenum. Small intestine. Colon. Rectum. Anus
Tumors
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Summary:Mucinous colorectal cancer (CRC) has been reported to have distinct clinicopathological and genetic characteristics. However, the incidence and the relationship among microsatellite instability (MSI), CpG island methylator phenotype (CIMP) and BRAF and KRAS mutations in mucinous and non‐mucinous CRC are not known. Activating mutations of BRAF and KRAS and their relationship with MSI and CIMP were examined in 83 sporadic CRC specimens (26 mucinous and 57 non‐mucinous CRC). MSI, CIMP, BRAF and KRAS mutation were observed in 17, 24, 25 and 36% of the tumors, respectively. BRAF mutation was highly correlated with MSI (p < 0.001) and CIMP (p < 0.001). A higher incidence of MSI (27% vs. 12%), CIMP (38% vs. 18%, p < 0.05) and BRAF mutation (46% vs. 16%, p < 0.01) was observed in mucinous CRC. KRAS mutation (27% vs. 40%) was observed more frequently in non‐mucinous CRC. Significantly higher percentages of mucinous CRC (54%, p < 0.05) had MSI or CIMP or BRAF mutations. Concordant occurrence of 2 or more of these alterations was observed in 39% of mucinous CRC and only 11% of non‐mucinous CRC (p < 0.01). The more frequent occurrence and closer association among MSI, CIMP and BRAF mutation in mucinous CRC observed in our study further supports the idea that its pathogenesis may involve distinct genetic and epigenetic changes. © 2005 Wiley‐Liss, Inc.
ISSN:0020-7136
1097-0215
DOI:10.1002/ijc.21701