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Molecular Cancer
Published in: Molecular Cancer 1/2014

Open Access 01-12-2014 | Research

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

Authors: Abdul K Siraj, Rong Bu, Sarita Prabhakaran, Prashant Bavi, Shaham Beg, Mohsen Al Hazmi, Maha Al-Rasheed, Khadija Alobaisi, Fouad Al-Dayel, Hadeel AlManea, Nasser Al-Sanea, Shahab Uddin, Khawla S Al-Kuraya

Published in: Molecular Cancer | Issue 1/2014

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Abstract

Background

Recent 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.

Methods

770 CRC cases were analyzed for BRAF and KRAS mutations by direct DNA sequencing.

Results

BRAF 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).

Conclusion

Our 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.
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Metadata
Title
A very low incidence of BRAF mutations in Middle Eastern colorectal carcinoma
Authors
Abdul K Siraj
Rong Bu
Sarita Prabhakaran
Prashant Bavi
Shaham Beg
Mohsen Al Hazmi
Maha Al-Rasheed
Khadija Alobaisi
Fouad Al-Dayel
Hadeel AlManea
Nasser Al-Sanea
Shahab Uddin
Khawla S Al-Kuraya
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2014
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/1476-4598-13-168

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