title: Analysis of colorectal cancers in British Bangladeshi identifies early onset, frequent mucinous histotype and a high prevalence of RBFOX1 deletion.
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.
authors.affiliation: Centre for Digestive Diseases, Blizard Institute of Cell and Molecular Science, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, 4 Newark St, Whitechapel, London, E1 2AT, UK.
authors.forename: Neel
authors.initials: N
authors.lastname: Sengupta
authors.forename: Christopher
authors.initials: C
authors.lastname: Yau
authors.forename: Anuratha
authors.initials: A
authors.lastname: Sakthianandeswaren
authors.forename: Dmitri
authors.initials: D
authors.lastname: Mouradov
authors.forename: Peter
authors.initials: P
authors.lastname: Gibbs
authors.forename: Nirosha
authors.initials: N
authors.lastname: Suraweera
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Cazier
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Polanco-Echeverry
authors.forename: Anil
authors.initials: A
authors.lastname: Ghosh
authors.forename: Mohamed
authors.initials: M
authors.lastname: Thaha
authors.forename: Shafi
authors.initials: S
authors.lastname: Ahmed
authors.forename: Roger
authors.initials: R
authors.lastname: Feakins
authors.forename: David
authors.initials: D
authors.lastname: Propper
authors.forename: Sina
authors.initials: S
authors.lastname: Dorudi
authors.forename: Oliver
authors.initials: O
authors.lastname: Sieber
authors.forename: Andrew
authors.initials: A
authors.lastname: Silver
authors.forename: Cecilia
authors.initials: C
authors.lastname: Lai
mesh_terms: D002288:Adenocarcinoma, Mucinous / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001459:Bangladesh / Q000208:ethnology; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism; D004252:DNA Mutational Analysis; D005260:Female; D017353:Gene Deletion; D018628:Gene Dosage; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011518:Proto-Oncogene Proteins / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D000072260:RNA Splicing Factors; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D006113:United Kingdom; D044465:White People; D055815:Young Adult; D018631:ras Proteins / Q000235:genetics
chemical_list: C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C455479:RBFOX1 protein, human; D000072260:RNA Splicing Factors; D016601:RNA-Binding Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins