Cancer arises from a multi‑step cellular transformation process where some mutations may be inherited, while others are acquired during the process of malignant transformation. Aberrations in the BCL2 associated transcription factor 1 (BCLAF1) gene have previously been identified in patients with cancer and the aim of the present study was to identify structural variants (SVs) and the effects of BCLAF1 gene silencing on cell transformation. Whole‑genome sequencing was performed on DNA isolated from tumour biopsies with a histologically confirmed diagnosis of oesophageal squamous cell carcinoma (OSCC). Paired‑end sequencing was performed on the Illumina HiSeq2000, with 300 bp reads. Reads were aligned to the Homo sapiens reference genome (NCBI37) using ELAND and CASAVA software. SVs reported from the alignment were collated with gene loci, using the variant effect predictor of Ensembl. The affected genes were subsequently cross‑checked against the Genetic Association Database for disease and cancer associations. BCLAF1 deletion was identified as a noteworthy SV that could be associated with OSCC. Transient small interfering RNA‑mediated knockdown of BCLAF1 resulted in the altered expression of several downstream genes, including downregulation of the proapoptotic genes Caspase‑3 and BAX and the DNA damage repair genes exonuclease 1, ATR‑interacting protein and transcription regulator protein BACH1. BCLAF1 deficiency also attenuated P53 gene expression. Inhibition of BCLAF1 expression also resulted in increased colony formation. These results provide evidence that the abrogation of BCLAF1 expression results in the dysregulation of several cancer signalling pathways and abnormal cell proliferation.

中文翻译：

---

全基因组测序的新见解：BCLAF1 缺失是一种结构变异，使细胞易于发生细胞转化。

癌症起源于一个多步骤的细胞转化过程，其中一些突变可能是遗传的，而另一些则是在恶性转化过程中获得的。先前已在癌症患者中发现BCL2 相关转录因子 1 ( BCLAF1 ) 基因的异常，本研究的目的是确定结构变异 (SV) 和BCLAF1的影响细胞转化的基因沉默。对从组织学确诊为食管鳞状细胞癌 (OSCC) 的肿瘤活检组织中分离的 DNA 进行全基因组测序。双末端测序在 Illumina HiSeq2000 上进行，读数为 300 bp。使用 ELAND 和 CASAVA 软件将读数与智人参考基因组 (NCBI37) 对齐。使用 Ensembl 的变体效应预测器将比对报告的 SV 与基因位点进行核对。随后将受影响的基因与疾病和癌症关联的遗传关联数据库进行了交叉检查。BCLAF1缺失被确定为可能与 OSCC 相关的值得注意的 SV。瞬时小干扰 RNA 介导的BCLAF1敲低导致几个下游基因的表达改变，包括促凋亡基因 Caspase-3 和 BAX 以及 DNA 损伤修复基因外切核酸酶 1、ATR 相互作用蛋白和转录调节蛋白 BACH1 的下调。BCLAF1缺乏也减弱了 P53 基因的表达。BCLAF1表达的抑制也导致集落形成增加。这些结果提供了证据，表明BCLAF1表达的消除导致几种癌症信号通路的失调和异常的细胞增殖。