Analysis of colorectal cancers in British Bangladeshi identifies early onset, frequent mucinous histotype and a high prevalence of RBFOX1 deletion

Sengupta, N; Yau, C; Sakthianandeswaren, A; Mouradov, D; Gibbs, P; Suraweera, N; Cazier, JB; Polanco-Echeverry, G; Ghosh, A; Thaha, M; Ahmed, S; Feakins, R; Propper, D; Dorudi, S; Sieber, O; Silver, A; Lai, C

Author(s): Sengupta, N; Yau, C; Sakthianandeswaren, A; Mouradov, D; Gibbs, P; Suraweera, N; Cazier, JB; Polanco-Echeverry, G; Ghosh, A; Thaha, M; Ahmed, S; Feakins, R; Propper, D; Dorudi, S; Sieber, O; Silver, A; Lai, C;
Journal Title: Molecular Cancer
Publication Type: Journal Article
Abstract: BACKGROUND: Prevalence of colorectal cancer (CRC) in the British Bangladeshi population (BAN) is low compared to British Caucasians (CAU). Genetic background may influence mutations and disease features. METHODS: We characterized the clinicopathological features of BAN CRCs and interrogated their genomes using mutation profiling and high-density single nucleotide polymorphism (SNP) arrays and compared findings to CAU CRCs. RESULTS: Age of onset of BAN CRC was significantly lower than for CAU patients (p=3.0 x 10-5) and this difference was not due to Lynch syndrome or the polyposis syndromes. KRAS mutations in BAN microsatellite stable (MSS) CRCs were comparatively rare (5.4%) compared to CAU MSS CRCs (25%; p=0.04), which correlates with the high percentage of mucinous histotype observed (31%) in the BAN samples. No BRAF mutations was seen in our BAN MSS CRCs (CAU CRCs, 12%; p=0.08). Array data revealed similar patterns of gains (chromosome 7 and 8q), losses (8p, 17p and 18q) and LOH (4q, 17p and 18q) in BAN and CAU CRCs. A small deletion on chromosome 16p13.2 involving the alternative splicing factor RBFOX1 only was found in significantly more BAN (50%) than CAU CRCs (15%) cases (p=0.04). Focal deletions targeting the 5' end of the gene were also identified. Novel RBFOX1 mutations were found in CRC cell lines and tumours; mRNA and protein expression was reduced in tumours. CONCLUSIONS: KRAS mutations were rare in BAN MSS CRC and a mucinous histotype common. Loss of RBFOX1 may explain the anomalous splicing activity associated with CRC.
Publisher: BioMed Central
Research Division(s): Systems Biology And Personalised Medicine
Link To PubMed Central Version: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3544714/
Publisher's Version: https://doi.org/10.1186/1476-4598-12-1
Open Access at Publisher's Site: http://www.molecular-cancer.com/content/12/1/1
Terms of Use/Rights Notice: © 2013 Sengupta et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Creation Date: 2014-02-07 03:29:58