RNA sequencing of esophageal adenocarcinomas identifies novel fusion transcripts, including NPC1-MELK, arising from a complex chromosomal rearrangement.
RNA sequencing of esophageal adenocarcinomas identifies novel fusion transcripts, including NPC1-MELK, arising from a complex chromosomal rearrangement.
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DOI：
10.1002/cncr.30837
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发表时间：
2017-10-15
期刊：
影响因子：
6.2
通讯作者：
Meltzer SJ
中科院分区：
文献类型：
--
作者：
Wang Z;Cheng Y;Abraham JM;Yan R;Liu X;Chen W;Ibrahim S;Schroth GP;Ke X;He Y;Meltzer SJ
对染色体重排和融合转录本的研究已经阐明了肿瘤发生的机制，并导致了有针对性的癌症治疗。在这项研究中，我们的目标是在食管腺癌中发现新的融合转录本。为了确定与食管腺癌相关的新的融合转录本，我们对40例食管腺癌(EAC)和来自相同患者的匹配的非恶性标本进行了靶向RNA测序和PCR验证。用基因组聚合酶链式反应和Sanger测序寻找融合基因的断裂点。在40个EAC以及另外15个EAC(总共55名患者)的验证队列中发现并验证了5个新的框内融合转录本：FGFR2-GAB2(2/55，或3.6%)、NPC1-Melk(2/55，或3.6%)、USP54-CAMK2G(2/55，或3.6%)、MKL1-FBLN1(1/55，或1.8%)和CNOT2-C12orf49(1/55，或1.8%)。基因组分析表明，NPC1-Melk起源于一种复杂的染色体间易位事件，涉及18号、3号和9号染色体，具有3个重组点，与染色质一致。这些数据表明，融合转录本在EAC中以稳定的频率出现。此外，我们的结果表明，染色体复合体是在EAC中产生融合转录本的一种潜在机制。这些和其他融合转录本作为EAC的诊断标志物和潜在的治疗靶点值得进一步研究。
Studies of chromosomal rearrangements and fusion transcripts have elucidated mechanisms of tumorigenesis and led to targeted cancer therapies. In this study, we aimed to identify novel fusion transcripts in esophageal adenocarcinomas. To identify new fusion transcripts associated with esophageal adenocarcinoma, we performed targeted RNA sequencing and PCR verification in 40 esophageal adenocarcinomas (EACs) and matched non-malignant specimens from the same patients. Genomic PCR and Sanger sequencing were performed to find the breakpoint of fusion genes. Five novel in-frame fusion transcripts were identified and verified in 40 EACs as well as in a validation cohort of 15 additional EACs (in total, 55 patients): FGFR2-GAB2 (2/55, or 3.6%), NPC1-MELK (2/55, or 3.6%), USP54-CAMK2G (2/55, or 3.6%), MKL1-FBLN1 (1/55, or 1.8%), and CNOT2-C12orf49 (1/55, or 1.8%). Genomic analysis indicated that NPC1-MELK arose from a complex inter-chromosomal translocation event involving chromosomes 18, 3, and 9 with three rearrangement points, consistent with chromoplexy. These data indicate that fusion transcripts occur at a stable frequency in EAC. Furthermore, our results indicate that chromoplexy is an underlying mechanism that generates fusion transcripts in EAC. These and other fusion transcripts merit further study as diagnostic markers and potential therapeutic targets in EAC.
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影响因子：
3.7
作者：
Frankel, Adam;Armour, Nicola;Barbour, Andrew
通讯作者：
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Kloosterman, Wigard P.;Guryev, Victor;Cuppen, Edwin
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11.2
作者：
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通讯作者：
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