Cancer Biology and Pharmacology, Genome Institute of Singapore, Genome, Singapore 138672, Singapore.
Genome Res. 2011 May;21(5):676-87. doi: 10.1101/gr.113225.110. Epub 2011 Apr 5.
Using a long-span, paired-end deep sequencing strategy, we have comprehensively identified cancer genome rearrangements in eight breast cancer genomes. Herein, we show that 40%-54% of these structural genomic rearrangements result in different forms of fusion transcripts and that 44% are potentially translated. We find that single segmental tandem duplication spanning several genes is a major source of the fusion gene transcripts in both cell lines and primary tumors involving adjacent genes placed in the reverse-order position by the duplication event. Certain other structural mutations, however, tend to attenuate gene expression. From these candidate gene fusions, we have found a fusion transcript (RPS6KB1-VMP1) recurrently expressed in ∼30% of breast cancers associated with potential clinical consequences. This gene fusion is caused by tandem duplication on 17q23 and appears to be an indicator of local genomic instability altering the expression of oncogenic components such as MIR21 and RPS6KB1.
采用长片段、配对末端深度测序策略，我们全面鉴定了 8 例乳腺癌基因组中的癌症基因组重排。本研究表明，这些结构基因组重排中有 40%-54%导致不同形式的融合转录本，其中 44%可能被翻译。我们发现，跨越几个基因的单片段串联重复是细胞系和原发性肿瘤中融合基因转录本的主要来源，这些融合基因转录本涉及通过重复事件反向排列的邻近基因。然而，某些其他结构突变往往会减弱基因表达。从这些候选基因融合中，我们发现了一种融合转录本（RPS6KB1-VMP1），在约 30%与潜在临床后果相关的乳腺癌中反复表达。这种基因融合是由于 17q23 上的串联重复引起的，似乎是局部基因组不稳定性的标志物，改变了致癌成分（如 MIR21 和 RPS6KB1）的表达。
