Mutation profile of KRAS and BRAF genes in patients with colorectal cancer: association with morphological and prognostic criteria
| Autor: | Maria Samara, Papamichali R, C Papandreou, A Athanasiadis, Georgios K. Koukoulis, Evanthia Kostopoulou, K. Kapatou, Maria Ioannou |
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| Rok vydání: | 2015 |
| Předmět: |
Male
Proto-Oncogene Proteins B-raf endocrine system diseases Adenoma Colorectal cancer DNA Mutational Analysis medicine.disease_cause Exon Genetics medicine Humans Point Mutation Codon neoplasms Molecular Biology Gene Neoplasm Staging Mutation business.industry Point mutation Exons General Medicine Prognosis medicine.disease digestive system diseases Amino Acid Substitution ras Proteins Mutation testing Cancer research Female KRAS Neoplasm Grading Colorectal Neoplasms business |
| Zdroj: | Genetics and Molecular Research. 14:16793-16802 |
| ISSN: | 1676-5680 |
| DOI: | 10.4238/2015.december.14.6 |
| Popis: | KRAS and BRAF mutations are well-recognized molecular alterations during colorectal carcinogenesis, but there is little agreement on their effect on tumor characteristics. Therefore, we aimed to evaluate the distribution of the most common KRAS and BRAF mutations in Greek patients with colorectal cancer and their possible associations with clinical histopathological parameters. In this study, 322 and 188 colorectal carcinomas were used for the mutation analysis of KRAS (exon 2) and BRAF (exon 15) genes, respectively. The mutational status of both genes was evaluated by polymerase chain reaction and sequencing analysis. Although the overall frequency of KRAS mutations (36.6%) seemed to be similar to those reported for other populations, the rate of point mutations at codon 13 was significantly lower (12%) in Greek patients with colorectal cancer and associated with male gender (P0.05). Tumors with GT codon 12 transversions and GC transitions showed more frequent lymph node metastasis (P0.05, P0.005, respectively). The rate of KRAS mutations gradually decreased with increasing histological grade (P0.05), as opposed to BRAF mutations, which were strongly associated with poorly differentiated tumors (P0.005). Additionally, we found that the histological features of preexisting adenoma were associated with the absence of BRAF mutations, in contrast to KRAS (P0.05). Our data suggested that there seems to be a correlation between morphological criteria and discrete genetic pathways in colorectal carcinogenesis. Moreover, ethnic or geographic factors may have an impact on genetic background of colorectal carcinomas, and specific types of KRAS mutations may influence the metastatic potential of colorectal tumors. |
| Databáze: | OpenAIRE |
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