Laddha Saurabh V, Ganesan Shridar, Chan Chang S, White Eileen
Rutgers Cancer Institute of New Jersey, 195 Little Albany Street, New Brunswick, NJ 08903-2681.
Mol Cancer Res. 2014 Apr;12(4):485-90. doi: 10.1158/1541-7786.MCR-13-0614. Epub 2014 Jan 29.
Evidence suggests that the catabolic process of macroautophagy (autophagy hereafter) can either suppress or promote cancer. The essential autophagy gene ATG6/BECN1 encoding the Beclin1 protein has been implicated as a haploinsufficient tumor suppressor in breast, ovarian, and prostate cancers. The proximity of BECN1 to the known breast and ovarian tumor suppressor breast cancer 1, early onset, BRCA1, on chromosome 17q21, has made this determination equivocal. Here, the mutational status of BECN1 was assessed in human tumor sequencing data from The Cancer Genome Atlas (TCGA) and other databases. Large deletions encompassing both BRCA1 and BECN1, and deletions of only BRCA1 but not BECN1, were found in breast and ovarian cancers, consistent with BRCA1 loss being a primary driver mutation in these cancers. Furthermore, there was no evidence for BECN1 mutation or loss in any other cancer, casting doubt on whether BECN1 is a tumor suppressor in most human cancers.
Contrary to previous reports, BECN1 is not significantly mutated in human cancer and not a tumor-suppressor gene, as originally thought. VISUAL OVERVIEW: http://mcr.aacrjournals.org/content/early/2014/04/01/1541-7786.MCR-13-0614/F1.large.jpg.
有证据表明，巨自噬（以下简称自噬）的分解代谢过程既可以抑制癌症，也可以促进癌症。编码Beclin1蛋白的自噬关键基因ATG6/BECN1在乳腺癌、卵巢癌和前列腺癌中被认为是单倍体不足的肿瘤抑制因子。BECN1与位于17q21染色体上已知的乳腺癌和卵巢癌肿瘤抑制因子乳腺癌1号基因（早发型）BRCA1位置接近，这使得这一判定存在疑问。在此，对来自癌症基因组图谱（TCGA）和其他数据库的人类肿瘤测序数据中BECN1的突变状态进行了评估。在乳腺癌和卵巢癌中发现了同时包含BRCA1和BECN1的大片段缺失，以及仅BRCA1缺失而BECN1未缺失的情况，这与BRCA1缺失是这些癌症的主要驱动突变一致。此外，没有证据表明在任何其他癌症中存在BECN1突变或缺失，这让人怀疑BECN1在大多数人类癌症中是否为肿瘤抑制因子。
与之前的报道相反，BECN1在人类癌症中没有明显突变，并非如最初认为的那样是一个肿瘤抑制基因。视觉概述：http://mcr.aacrjournals.org/content/early/2014/04/01/1541-7786.MCR-13-0614/F1.large.jpg。
