Identification of fusion genes in breast cancer by paired-end RNA-sequencing.
Identification of fusion genes in breast cancer by paired-end RNA-sequencing.
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DOI：
10.1186/gb-2011-12-1-r6
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发表时间：
2011
期刊：
影响因子：
12.3
通讯作者：
Kallioniemi O
中科院分区：
文献类型：
--
作者：
Edgren H;Murumagi A;Kangaspeska S;Nicorici D;Hongisto V;Kleivi K;Rye IH;Nyberg S;Wolf M;Borresen-Dale AL;Kallioniemi O
直到最近，染色体易位和融合基因一直是实体瘤中未被充分认识的一类突变。下一代测序技术为系统表征癌细胞转录组提供了机会，包括发现由潜在基因组重排引起的表达融合基因。我们应用对端RNA-seq技术鉴定了乳腺癌细胞中24个新的融合基因和3个已知的融合基因。在改进的生物信息学方法的支持下，我们对最初通过RNA-seq检测到的基因融合的验证成功率为95%。发现融合伴侣基因提供启动子（5' UTR）、编码序列和3' UTR。大多数融合基因与拷贝数转换有关，在高水平DNA扩增中尤其常见。这表明融合事件可能有助于DNA扩增和缺失所提供的选择优势。一些融合伴侣基因，如TATDN1-GSDMB融合中的GSDMB和VAPB-IKZF3融合中的IKZF3，仅作为融合转录物被检测到，这表明融合事件激活了一个休眠基因。许多融合基因伴侣要么在先前的致癌基因融合中被观察到，主要是在白血病中，要么被报道为致癌。RNA干扰介导的VAPB-IKZF3融合基因敲低表明它可能是癌细胞生长和存活所必需的。综上所述，通过rna测序和改进的生物信息学分层，我们在乳腺癌中发现了许多新的融合基因，并确定了VAPB-IKZF3是一个潜在的融合基因，对乳腺癌细胞的生长和存活具有重要意义。
Until recently, chromosomal translocations and fusion genes have been an underappreciated class of mutations in solid tumors. Next-generation sequencing technologies provide an opportunity for systematic characterization of cancer cell transcriptomes, including the discovery of expressed fusion genes resulting from underlying genomic rearrangements. We applied paired-end RNA-seq to identify 24 novel and 3 previously known fusion genes in breast cancer cells. Supported by an improved bioinformatic approach, we had a 95% success rate of validating gene fusions initially detected by RNA-seq. Fusion partner genes were found to contribute promoters (5' UTR), coding sequences and 3' UTRs. Most fusion genes were associated with copy number transitions and were particularly common in high-level DNA amplifications. This suggests that fusion events may contribute to the selective advantage provided by DNA amplifications and deletions. Some of the fusion partner genes, such as GSDMB in the TATDN1-GSDMB fusion and IKZF3 in the VAPB-IKZF3 fusion, were only detected as a fusion transcript, indicating activation of a dormant gene by the fusion event. A number of fusion gene partners have either been previously observed in oncogenic gene fusions, mostly in leukemias, or otherwise reported to be oncogenic. RNA interference-mediated knock-down of the VAPB-IKZF3 fusion gene indicated that it may be necessary for cancer cell growth and survival. In summary, using RNA-sequencing and improved bioinformatic stratification, we have discovered a number of novel fusion genes in breast cancer, and identified VAPB-IKZF3 as a potential fusion gene with importance for the growth and survival of breast cancer cells.
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影响因子：
11.2
作者：
Iljin, Kristiina;Wolf, Maija;Kallioniemi, Olli
通讯作者：
Kallioniemi, Olli
影响因子：
17.1
作者：
Leary RJ;Kinde I;Diehl F;Schmidt K;Clouser C;Duncan C;Antipova A;Lee C;McKernan K;De La Vega FM;Kinzler KW;Vogelstein B;Diaz LA Jr;Velculescu VE
通讯作者：
Velculescu VE
DOI：
10.1038/nrc1299
发表时间：
2004-03
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
通讯作者：
--
影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
影响因子：
7.5
作者：
Lae, Marick;Freneaux, Paul;Vincent-Salomon, Anne
通讯作者：
Vincent-Salomon, Anne