A very low incidence of BRAF mutations in Middle Eastern colorectal carcinoma

Molecular Cancer

Research

Nasser Al-Sanea¹  Fouad Al-Dayel²  Hadeel AlManea²  Shahab Uddin³  Mohsen Al Hazmi³  Prashant Bavi³  Khadija Alobaisi³  Rong Bu³  Abdul K Siraj³  Shaham Beg³  Sarita Prabhakaran³  Maha Al-Rasheed³  Khawla S Al-Kuraya⁴ 

[1] Colorectal Unit, Department of Surgery, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia;Department of Pathology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia;Human Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Center, P.O. Box 3354, MBC#98-16, 11211, Riyadh, Saudi Arabia;Human Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Center, P.O. Box 3354, MBC#98-16, 11211, Riyadh, Saudi Arabia;Department of Pathology, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia;

关键词: Colorectal cancer;    BRAF;    KRAS;    Microsatellite instability (MSI);    Lynch Syndrome (LS);    Hereditary non polyposis colorectal cancer (HNPCC) syndrome;   

DOI  :  10.1186/1476-4598-13-168

 received in 2014-04-27, accepted in 2014-06-24,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundRecent studies emphasize the role of BRAF as a genetic marker for prediction, prognosis and risk stratification in colorectal cancer. Earlier studies have reported the incidence of BRAF mutations in the range of 5-20% in colorectal carcinomas (CRC) and are predominantly seen in the serrated adenoma-carcinoma pathway characterized by microsatellite instability (MSI-H) and hypermethylation of the MLH1 gene in the setting of the CpG island methylator phenotype (CIMP). Due to the lack of data on the true incidence of BRAF mutations in Saudi Arabia, we sought to analyze the incidence of BRAF mutations in this ethnic group.Methods770 CRC cases were analyzed for BRAF and KRAS mutations by direct DNA sequencing.ResultsBRAF gene mutations were seen in 2.5% (19/757) CRC analyzed and BRAF V600E somatic mutation constituted 90% (17/19) of all BRAF mutations. BRAF mutations were significantly associated with right sided tumors (p = 0.0019), MSI-H status (p = 0.0144), CIMP (p = 0.0017) and a high proliferative index of Ki67 expression (p = 0.0162). Incidence of KRAS mutations was 28.6% (216/755) and a mutual exclusivity was noted with BRAF mutations (p = 0.0518; a trend was seen).ConclusionOur results highlight the low incidence of BRAF mutations and CIMP in CRC from Saudi Arabia. This could be attributed to ethnic differences and warrant further investigation to elucidate the effect of other environmental and genetic factors. These findings indirectly suggest the possibility of a higher incidence of familial hereditary colorectal cancers especially Hereditary non polyposis colorectal cancer (HNPCC) syndrome /Lynch Syndrome (LS) in Saudi Arabia.

【 授权许可】

Unknown   
© Siraj et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.