title: Novel FAM134B mutations and their clinicopathological significance in colorectal cancer.
abstract: FAM134B is a putative tumour suppressor gene and no mutations in FAM134B have been reported in colorectal cancer (CRC) to date. This study aims to identify FAM134B mutation sites and the clinicopathological significance of the gene in patients with CRC. Eighty-eight colorectal cancers were studied for FAM134B mutations by Sanger sequencing. The mutations in these cancers were then tested for correlations with the clinical and pathological parameters of the studied cancers. In addition, mRNA and protein expression of FAM134B in colorectal cancers was examined by polymerase chain reaction, Western blots, and immunofluorescence analysis. FAM134B mutation was noted in 46.5% (41/88) of patients with CRC. Thirty-one novel potentially pathogenic mutations were noted in coding and intronic regions of FAM134B in CRC, the majority of which were single-nucleotide substitutions. Of the 31 mutations, eight novel frameshift mutations showed potential to cause non-sense-mediated mRNA decay (NMD) in computational analysis. In addition, FAM134B mutations were associated with various clinical and pathological variables, including sex of the patients, presence of metachronous cancer, size, T staging, presence of distant metastases, and positivity of microsatellite instability (MSI) in the cancer (p < 0.05). FAM134B mRNA and protein expression was decreased in FAM134B mutated cancers. To conclude, FAM134B mutation is common in colorectal cancer. The association of the mutation of this gene with adverse clinical and pathological parameters is congruent with the tumour suppressive properties of the gene.
authors.affiliation: Cancer Molecular Pathology, School of Medicine and Griffith Health Institute, Griffith University, Gold Coast Campus, Gold Coast, QLD, 4222, Australia.
authors.forename: Farhadul
authors.initials: F
authors.lastname: Islam
authors.affiliation: Cancer Molecular Pathology, School of Medicine and Griffith Health Institute, Griffith University, Gold Coast Campus, Gold Coast, QLD, 4222, Australia.
authors.forename: Vinod
authors.initials: V
authors.lastname: Gopalan
authors.affiliation: Cancer Molecular Pathology, School of Medicine and Griffith Health Institute, Griffith University, Gold Coast Campus, Gold Coast, QLD, 4222, Australia.
authors.forename: Riajul
authors.initials: R
authors.lastname: Wahab
authors.affiliation: Cancer Molecular Pathology, School of Medicine and Griffith Health Institute, Griffith University, Gold Coast Campus, Gold Coast, QLD, 4222, Australia.
authors.forename: Katherine Ting-Wei
authors.initials: KT
authors.lastname: Lee
authors.affiliation: Cancer Molecular Pathology, School of Medicine and Griffith Health Institute, Griffith University, Gold Coast Campus, Gold Coast, QLD, 4222, Australia.
authors.forename: Md Hakimul
authors.initials: MH
authors.lastname: Haque
authors.affiliation: Cancer Molecular Pathology, School of Medicine and Griffith Health Institute, Griffith University, Gold Coast Campus, Gold Coast, QLD, 4222, Australia.
authors.forename: Afraa
authors.initials: A
authors.lastname: Mamoori
authors.affiliation: Department of Surgery, Gold Coast Hospital, Gold Coast, QLD, Australia.
authors.forename: Cu-Tai
authors.initials: CT
authors.lastname: Lu
authors.affiliation: Cancer Molecular Pathology, School of Medicine and Griffith Health Institute, Griffith University, Gold Coast Campus, Gold Coast, QLD, 4222, Australia.|Faculty of Health, Genomics Research Centre, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD, Australia.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Smith
authors.affiliation: Cancer Molecular Pathology, School of Medicine and Griffith Health Institute, Griffith University, Gold Coast Campus, Gold Coast, QLD, 4222, Australia. a.lam@griffith.edu.au.
authors.forename: Alfred K-Y
authors.initials: AK
authors.lastname: Lam
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; C522691:RETREG1 protein, human; D012333:RNA, Messenger