Islam Farhadul, Gopalan Vinod, Wahab Riajul, Lee Katherine Ting-Wei, Haque Md Hakimul, Mamoori Afraa, Lu Cu-Tai, Smith Robert A, Lam Alfred K-Y
Cancer Molecular Pathology, School of Medicine and Griffith Health Institute, Griffith University, Gold Coast Campus, Gold Coast, QLD, 4222, Australia.
Department of Surgery, Gold Coast Hospital, Gold Coast, QLD, Australia.
Hum Genet. 2017 Mar;136(3):321-337. doi: 10.1007/s00439-017-1760-4. Epub 2017 Jan 31.
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.
FAM134B是一种假定的肿瘤抑制基因，迄今为止，尚未有关于结直肠癌（CRC）中FAM134B突变的报道。本研究旨在确定FAM134B的突变位点以及该基因在CRC患者中的临床病理意义。通过桑格测序研究了88例结直肠癌中的FAM134B突变。然后测试这些癌症中的突变与所研究癌症的临床和病理参数之间的相关性。此外，通过聚合酶链反应、蛋白质免疫印迹和免疫荧光分析检测了结直肠癌中FAM134B的mRNA和蛋白表达。在46.5%（41/88）的CRC患者中发现了FAM134B突变。在CRC中，FAM134B的编码区和内含子区域发现了31个新的潜在致病突变，其中大多数是单核苷酸替换。在这31个突变中，8个新的移码突变在计算机分析中显示出导致无义介导的mRNA降解（NMD）的可能性。此外，FAM134B突变与各种临床和病理变量相关，包括患者性别、异时性癌的存在、大小、T分期、远处转移的存在以及癌症中微卫星不稳定性（MSI）的阳性（p<0.05）。在FAM134B突变的癌症中，FAM134B的mRNA和蛋白表达降低。总之，FAM134B突变在结直肠癌中很常见。该基因突变与不良临床和病理参数的关联与该基因的肿瘤抑制特性一致。
