《英文文献/摘要翻译》站在时间尽头2012

17、Significantly mutated genes

　　In CTNNB1, we identified a recurrent in-frame deletion of the complete exon 3 in 12 samples, 9 of which are colorectal cancers.
　　在CTNNB1基因中，我们在12个样本——其中9个是结直肠癌——中确定了三个样本有同样的周期性完整外显子的框内缺失。

　　（框内缺失：在基因翻译过程中，每三个核苷酸为一组，组成一个密码子，如果一个完整密码子被删除，而其他密码子可以正常翻译，这种突变就叫作框内缺失。）

　　Notably, these deletions were homozygous but thought to be activating as CTNNB1 normally acts as an oncogene in the WNT (Wingless / Integrated) and β-catenin pathway and none of these nine colorectal samples had any APC driver mutations.
　　值得注意的是，这些缺失是纯合的，但被认为是激活的，因为CTNNB1基因通常是WNT/β-catenin通路中的一个癌基因，而这9个结直肠样本均无APC（某肿瘤抑制基因）驱动突变。

　　（WNT信号通路广泛存在于无脊椎动物和脊椎动物中，是一类在物种进化过程中高度保守的信号通路。WNT信号在动物胚胎的早期发育、器官形成、组织再生和其它生理过程中，具有至关重要的作用。如果这条信号通路中的关键蛋白发生突变，导致信号异常活化，就可能诱导癌症的发生。

　　WNT是一类分泌型糖蛋白，通过自分泌或旁分泌发挥作用。WNT分泌后能与细胞表面特异性受体互相作用，通过一系列下游蛋白的磷酸化和去磷酸化过程，引起β-Catenin积累。β-Catenin是一种多功能的蛋白质，在细胞连接处与E-Cadherin相互作用，参与形成黏合带，而游离的β-Catenin可进入细胞核，调节基因表达，其异常表达或激活能引起肿瘤。）

　　We also identified several significantly deleted genes not previously reported, including MLLT4 and PARD3.
　　我们还确定了几个没有被报告过的显著缺失的基因，包括MLLT4和PARD3。

　　Unlike homozygous deletions, amplification peaks tend to be broad and often encompass large numbers of genes, making identification of the amplification target challenging.
　　不同于纯合子缺失，扩增的峰值往往范围广泛，时常包含大量的基因，使得扩增目标的确定具有了挑战性。

　　However, SOX4 stands out as a significantly amplified single gene peak and is highly enriched in urinary tract cancers.
　　然而，基因SOX4达到了单个基因显著扩增的峰值，因而十分突出，且在尿路癌中数量极多。

　　SOX4 is known to be overexpressed in prostate, hepatocel-lular, lung, bladder and medulloblastoma cancers with poor prognostic features and advanced disease status and is a modulator of the PI3K and Akt signalling pathway.
　　已知SOX4在前列腺癌、肝细胞癌、肺癌、膀胱癌和髓母细胞瘤中过度表达，具有不良的预后特征和晚期疾病境况，是PI3K和Akt信号通路的调节因子。

　　（PI3K/AKT及其相关通路在内化【外部生长因子和膜酪氨酸激酶】的作用方面非常重要。）

　　Also notable was a broad amplification peak of 10 genes around ZMIZ1 at 10q22.3, which has not previously been reported.
　　同样值得注意的是在10号染色体q22.3上，ZMIZ1周围10个基因的广泛扩增峰值，这是以前没有报道过的。

　　ZMIZ1 is a transcriptional coactivator of the protein inhibitor of activated STAT(signal transducer and activator of transcription)-like family and is a direct and selective cofactor of NOTCH1 in the development of T cells and leukaemia.
　　ZMIZ1是活性【信号传导和转录激活因子】族的抑制蛋白的转录共活性因子，是NOTCH1在T细胞生长和白血病进程中的一个直系选择性辅因子。

　　CDX2, previously identified as an amplified lineage-survival oncogene in colorectal cancer, is also highly amplified in our cohort with 20 out of 22 amplified samples found in colorectal cancer, representing 5.4% of all colorectal samples.
　　CDX2，以前被确定为大肠癌的扩增谱系—生存癌基因，在我们的队列中也高度扩增，在 22 个发现于大肠癌的扩增样本中有20个，占所有大肠癌样本（中扩增基因）的5.4%。