The novel fusion transcript NR5A2-KLHL29FT is generated by an insertion at the KLHL29 locus.
The novel fusion transcript NR5A2-KLHL29FT is generated by an insertion at the KLHL29 locus.
复制标题
新的融合转录本 NR5A2-KLHL29FT 是通过在 KLHL29 基因座插入而生成的。
DOI：
10.1002/cncr.30510
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发表时间：
2017
期刊：
影响因子：
6.2
通讯作者：
Meltzer,StephenJ
中科院分区：
文献类型：
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作者：
Sun,Zhenguo;Ke,Xiquan;Salzberg,StevenL;Kim,Daehwan;Antonescu,Valentin;Cheng,Yulan;Huang,Binbin;Song,JeeHoon;Abraham,JohnM;Ibrahim,Sariat;Tian,Hui;Meltzer,StephenJ
背景：由染色体重排引起的新型融合转录物（FTs）是癌症发生的常见因素。在目前的研究中，作者使用大量平行RNA测序来识别结肠癌中新的FTs。方法采用srna测序（RNA‐Seq）和TopHat‐Fusion技术鉴定结肠癌中新的FTs。然后，作者研究了新的FT核受体亚家族5，A组，成员2 (NR5A2) - Kelch样家族成员29FT （KLHL29FT）是否从基因组染色体重排中转录。接下来，通过定量实时聚合酶链反应检测NR5A2‐KLHL29FT在结肠癌和相应的正常上皮中的表达。结果作者在正常上皮和癌上皮中发现了NR5A2‐KLHL29FT。在研究该转录本时，出乎意料地发现，这是由于1号染色体上的NR5A2序列在2号染色体上的非特征多态生殖系插入到KLHL29位点，而不是染色体重排。这种生殖系插入发生在种群频率为0.40的情况下，似乎与癌症的发展没有关系。此外，在KLHL29基因位点插入NR5A2的样本中，NR5A2‐KLHL29FT的表达得到了验证，而在没有插入NR5A2的样本中，NR5A2‐KLHL29FT的表达没有得到验证。有趣的是，NR5A2‐KLH29FT在结肠癌中的表达水平明显低于匹配的正常结肠上皮（P= 0.029），这表明NR5A2‐KLH29FT可能参与了这种肿瘤类型的起源或进展。结论snr5a2‐KLHL29FT是由NR5A2序列多态性插入到KLHL29位点而产生的。NR5A2‐KLHL29FT可能影响结肠癌的起源或进展。此外，研究人员应该意识到，类似的FTs可能是由于基因组数据库中未正确注释的转染色体插入而发生的，特别是在当前的组装算法下。©2017美国癌症协会。
BACKGROUNDNovel fusion transcripts (FTs) caused by chromosomal rearrangement are common factors in the development of cancers. In the current study, the authors used massively parallel RNA sequencing to identify new FTs in colon cancers.METHODSRNA sequencing (RNA‐Seq) and TopHat‐Fusion were used to identify new FTs in colon cancers. The authors then investigated whether the novel FT nuclear receptor subfamily 5, group A, member 2 (NR5A2)‐Kelch‐like family member 29 FT (KLHL29FT) was transcribed from a genomic chromosomal rearrangement. Next, the expression of NR5A2‐KLHL29FT was measured by quantitative real‐time polymerase chain reaction in colon cancers and matched corresponding normal epithelia.RESULTSThe authors identified the FT NR5A2‐KLHL29FT in normal and cancerous epithelia. While investigating this transcript, it was unexpectedly found that it was due to an uncharacterized polymorphic germline insertion of the NR5A2 sequence from chromosome 1 into the KLHL29 locus at chromosome 2, rather than a chromosomal rearrangement. This germline insertion, which occurred at a population frequency of 0.40, appeared to bear no relationship to cancer development. Moreover, expression of NR5A2‐KLHL29FT was validated in RNA specimens from samples with insertions of NR5A2 at the KLHL29 gene locus, but not from samples without this insertion. It is interesting to note that NR5A2‐KLH29FT expression levels were significantly lower in colon cancers than in matched normal colonic epithelia (P=.029), suggesting the potential participation of NR5A2‐KLHL29FT in the origin or progression of this tumor type.CONCLUSIONSNR5A2‐KLHL29FT was generated from a polymorphism insertion of the NR5A2 sequence into the KLHL29 locus. NR5A2‐KLHL29FT may influence the origin or progression of colon cancer. Moreover, researchers should be aware that similar FTs may occur due to transchromosomal insertions that are not correctly annotated in genome databases, especially with current assembly algorithms.Cancer2017;123:1507–1515.©2017 American Cancer Society.