title: Identification of Novel FAM134B (JK1) Mutations in Oesophageal Squamous Cell Carcinoma.
abstract: Mutation of FAM134B (Family with Sequence Similarity 134, Member B) leading to loss of function of its encoded Golgi protein and has been reported induce apoptosis in neurological disorders. FAM134B mutation is still unexplored in cancer. Herein, we studied the DNA copy number variation and novel mutation sites of FAM134B in a large cohort of freshly collected oesophageal squamous cell carcinoma (ESCC) tissue samples. In ESCC tissues, 37% (38/102) showed increased FAM134B DNA copies whereas 35% (36/102) showed loss of FAM134B copies relative to matched non-cancer tissues. Novel mutations were detected in exons 4, 5, 7, 9 as well as introns 2, 4-8 of FAM134B via HRM (High-Resolution Melt) and Sanger sequencing analysis. Overall, thirty-seven FAM134B mutations were noted in which most (31/37) mutations were homozygous. FAM134B mutations were detected in all the cases with metastatic ESCC in the lymph node tested and in 14% (8/57) of the primary ESCC. Genetic alteration of FAM134B is a frequent event in the progression of ESCCs. These findings imply that mutation might be the major driving source of FAM134B genetic modulation in ESCCs.
authors.affiliation: Cancer Molecular Pathology in Menzies Health Institute Queensland, Griffith University, Gold Coast, Australia.
authors.forename: Md Hakimul
authors.initials: MH
authors.lastname: Haque
authors.affiliation: Cancer Molecular Pathology in Menzies Health Institute Queensland, Griffith University, Gold Coast, Australia.
authors.forename: Vinod
authors.initials: V
authors.lastname: Gopalan
authors.affiliation: Department of Pathology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong.
authors.forename: Kwok-Wah
authors.initials: KW
authors.lastname: Chan
authors.affiliation: School of Natural Sciences, Griffith University, Nathan Campus, Australia.
authors.forename: Muhammad J A
authors.initials: MJ
authors.lastname: Shiddiky
authors.affiliation: Cancer Molecular Pathology in Menzies Health Institute Queensland, Griffith University, Gold Coast, Australia.|Genomics Research Centre, Institute of Health and Biomedical Innovation, Faculty of Health, Queensland University of Technology, Brisbane, Queensland, Australia.
authors.forename: Robert Anthony
authors.initials: RA
authors.lastname: Smith
authors.affiliation: Cancer Molecular Pathology in Menzies Health Institute Queensland, Griffith University, Gold Coast, Australia.
authors.forename: Alfred King-Yin
authors.initials: AK
authors.lastname: Lam
mesh_terms: D001483:Base Sequence; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D056915:DNA Copy Number Variations / Q000235:genetics; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology; D000077277:Esophageal Squamous Cell Carcinoma; D005091:Exons / Q000235:genetics; D005260:Female; D005784:Gene Amplification; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007438:Introns / Q000235:genetics; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D009691:Nucleic Acid Denaturation; D015203:Reproducibility of Results
chemical_list: D004273:DNA, Neoplasm; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; C522691:RETREG1 protein, human