Novel fusion transcripts in human gastric cancer revealed by transcriptome analysis
Novel fusion transcripts in human gastric cancer revealed by transcriptome analysis
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DOI：
10.1038/onc.2013.490
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发表时间：
2014-11-20
期刊：
影响因子：
8
通讯作者：
Kim, T-Y
中科院分区：
文献类型：
--
作者：
Kim, H-P;Cho, G-A;Kim, T-Y
基因融合参与各种类型恶性肿瘤的发展。测序技术的最新进展促进了基因融合的鉴定，并刺激了这一领域在癌症中的研究。在本研究中，我们进行了下一代转录组测序，以发现胃癌中的新基因融合。通过生物信息学筛选，从12个胃癌细胞系中共检测到282个融合转录本候选物。在候选基因中，我们已经验证了19个融合转录本，其中7个是染色体间融合，12个是染色体内融合。在12个细胞系中的2个和13个胃癌组织中的10个中发现了新的DUS 4L-BCAP 29融合转录本。使用siRNA敲低DUS 4L-BCAP 29转录物抑制细胞增殖。软琼脂实验进一步证实了该融合基因具有致瘤性。我们还发现，microRNA编码基因PVT 1，这是在SNU-16细胞的双微小染色体扩增，是反复参与基因融合。PVT 1产生六种不同的融合转录本，涉及四种不同的基因作为融合伴侣。我们的研究结果提供了更好地了解胃癌的转录和遗传改变：即，转录通读和遗传不稳定的候选区域的致瘤作用。
Gene fusion is involved in the development of various types of malignancies. Recent advances in sequencing technology have facilitated identification of gene fusions and have stimulated the research of this field in cancer. In the present study, we performed next-generation transcriptome sequencing in order to discover novel gene fusions in gastric cancer. A total of 282 fusion transcript candidates were detected from 12 gastric cancer cell lines by bioinformatic filtering. Among the candidates, we have validated 19 fusion transcripts, which are 7 inter-chromosomal and 12 intra-chromosomal fusions. A novel DUS4L-BCAP29 fusion transcript was found in 2 out of 12 cell lines and 10 out of 13 gastric cancer tissues. Knockdown of DUS4L-BCAP29 transcript using siRNA inhibited cell proliferation. Soft agar assay further confirmed that this novel fusion transcript has tumorigenic potential. We also identified that microRNA-coding gene PVT1, which is amplified in double minute chromosomes in SNU-16 cells, is recurrently involved in gene fusion. PVT1 produced six different fusion transcripts involving four different genes as fusion partners. Our findings provide better insight into transcriptional and genetic alterations of gastric cancer: namely, the tumorigenic effects of transcriptional read-through and a candidate region for genetic instability.