Annala Matti, Taavitsainen Sinja, Vandekerkhove Gillian, Bacon Jack V W, Beja Kevin, Chi Kim N, Nykter Matti, Wyatt Alexander W
Faculty of Medicine and Life Sciences and Biomeditech Institute, University of Tampere, FI-33520, Tampere, Finland.
Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, Vancouver, BC, V6H 3Z6, Canada.
Commun Biol. 2018 Aug 24;1:122. doi: 10.1038/s42003-018-0128-1. eCollection 2018.
Prostate cancer has a low somatic mutation rate but non-coding regions remain underexplored. We sequenced the untranslated regions (UTRs) of 72 established driver genes in 428 patients with metastatic prostate cancer and identified 3'-UTR mutations in 12% of patients. The mutations were predominantly insertions or deletions, covered the entire UTR without motif enrichment, and were not detected in other cancers. lies in head-on orientation with the androgen-regulated non-coding gene , resulting in strong prostate lineage-specific bidirectional transcription across the 3'-UTR. This suggests transcriptional activity as a cause for the localized hypermutation. The indel-dominant pattern of somatic mutation extends into the coding region, where it is shaped by clonal selection to yield a cluster of non-frameshift indels inside the forkhead domain. Somatic 3'-UTR mutations may prove useful for diagnostic and screening approaches, given their high frequency and lineage specificity.
前列腺癌的体细胞突变率较低，但非编码区域仍未得到充分研究。我们对428例转移性前列腺癌患者中72个已确定的驱动基因的非翻译区（UTR）进行了测序，在12%的患者中发现了3'-UTR突变。这些突变主要是插入或缺失，覆盖了整个UTR，没有基序富集，且在其他癌症中未检测到。其与雄激素调节的非编码基因呈头对头方向排列，导致在3'-UTR上出现强烈的前列腺谱系特异性双向转录。这表明转录活性是局部高突变的原因。体细胞突变的插入缺失主导模式延伸到编码区，在那里它受到克隆选择的影响，在叉头结构域内产生一组非移码插入缺失。鉴于其高频率和谱系特异性，体细胞3'-UTR突变可能对诊断和筛查方法有用。
