Cancer Molecular Pathology in Menzies Health Institute Queensland, Griffith University, Gold Coast, Australia.
Department of Pathology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong.
Sci Rep. 2016 Jul 4;6:29173. doi: 10.1038/srep29173.
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.
FAM134B（家族与序列相似性 134，成员 B）的突变导致其编码的高尔基体蛋白功能丧失，并且已报道在神经紊乱中诱导细胞凋亡。FAM134B 突变在癌症中仍未被探索。在此，我们研究了一大组新采集的食管鳞状细胞癌（ESCC）组织样本中 FAM134B 的 DNA 拷贝数变异和新的突变位点。在 ESCC 组织中，37%（38/102）显示 FAM134B DNA 拷贝数增加，而 35%（36/102）显示 FAM134B 拷贝数相对于匹配的非癌组织丢失。通过 HRM（高分辨率熔解）和 Sanger 测序分析，在 FAM134B 的外显子 4、5、7、9 以及内含子 2、4-8 中检测到新的突变。总的来说，注意到 37 个 FAM134B 突变，其中大多数（31/37）突变是纯合的。在检测到的淋巴结转移性 ESCC 所有病例中以及在 14%（8/57）的原发性 ESCC 中检测到 FAM134B 突变。FAM134B 的遗传改变是 ESCC 进展中的常见事件。这些发现表明，突变可能是 ESCC 中 FAM134B 遗传调节的主要驱动源。
