Frequent mutation of the FOXA1 untranslated region in prostate cancer.
Frequent mutation of the FOXA1 untranslated region in prostate cancer.
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DOI：
10.1038/s42003-018-0128-1
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发表时间：
2018
影响因子：
5.9
通讯作者：
Wyatt AW
中科院分区：
文献类型：
--
作者：
Annala M;Taavitsainen S;Vandekerkhove G;Bacon JVW;Beja K;Chi KN;Nykter M;Wyatt AW
前列腺癌的体细胞突变率很低，但非编码区的研究仍然不足。我们对428例转移性前列腺癌患者的72个已建立的驱动基因的非翻译区(UTRs)进行了测序，并在12%的患者中发现了FOXA1 3‘-UTR突变。这些突变主要是插入或缺失，覆盖了整个非编码区，没有丰富的基序，在其他癌症中没有检测到。FOXA1与雄激素调节的非编码基因AL121790.1处于正面定位，导致FOXA1 3‘-UTR上有很强的前列腺系特异性双向转录。这表明转录活性是导致局部超突变的原因之一。体细胞突变的插入显性模式延伸到FOXA1编码区，在那里它是通过克隆选择来塑造的，在叉头域内产生一簇非移码的插入序列。体细胞FOXA1 3‘-UTR突变可能被证明是有用的诊断和筛查方法，因为它们的高频和谱系特异性。Matti Annala等人。报道前列腺癌中新的FOXA1突变的复发。这些位于3‘非翻译区的FOXA1突变可作为前列腺癌的诊断标记物。
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 FOXA1 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. FOXA1 lies in head-on orientation with the androgen-regulated non-coding gene AL121790.1, resulting in strong prostate lineage-specific bidirectional transcription across the FOXA1 3′-UTR. This suggests transcriptional activity as a cause for the localized hypermutation. The indel-dominant pattern of somatic mutation extends into the FOXA1 coding region, where it is shaped by clonal selection to yield a cluster of non-frameshift indels inside the forkhead domain. Somatic FOXA1 3′-UTR mutations may prove useful for diagnostic and screening approaches, given their high frequency and lineage specificity. Matti Annala et al. report the recurrence of new FOXA1 mutations in prostate cancer. These FOXA1 mutations in 3’ untranslated region may prove useful as diagnostic markers for prostate cancer.
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影响因子：
64.8
作者：
Nik-Zainal S;Davies H;Staaf J;Ramakrishna M;Glodzik D;Zou X;Martincorena I;Alexandrov LB;Martin S;Wedge DC;Van Loo P;Ju YS;Smid M;Brinkman AB;Morganella S;Aure MR;Lingjærde OC;Langerød A;Ringnér M;Ahn SM;Boyault S;Brock JE;Broeks A;Butler A;Desmedt C;Dirix L;Dronov S;Fatima A;Foekens JA;Gerstung M;Hooijer GK;Jang SJ;Jones DR;Kim HY;King TA;Krishnamurthy S;Lee HJ;Lee JY;Li Y;McLaren S;Menzies A;Mustonen V;O'Meara S;Pauporté I;Pivot X;Purdie CA;Raine K;Ramakrishnan K;Rodríguez-González FG;Romieu G;Sieuwerts AM;Simpson PT;Shepherd R;Stebbings L;Stefansson OA;Teague J;Tommasi S;Treilleux I;Van den Eynden GG;Vermeulen P;Vincent-Salomon A;Yates L;Caldas C;van't Veer L;Tutt A;Knappskog S;Tan BK;Jonkers J;Borg Å;Ueno NT;Sotiriou C;Viari A;Futreal PA;Campbell PJ;Span PN;Van Laere S;Lakhani SR;Eyfjord JE;Thompson AM;Birney E;Stunnenberg HG;van de Vijver MJ;Martens JW;Børresen-Dale AL;Richardson AL;Kong G;Thomas G;Stratton MR
通讯作者：
Stratton MR
影响因子：
48
作者：
Langmead, Ben;Salzberg, Steven L.
通讯作者：
Salzberg, Steven L.
影响因子：
64.5
作者：
Cancer Genome Atlas Research Network
通讯作者：
Cancer Genome Atlas Research Network
影响因子：
4.7
作者：
Robinson JL;Holmes KA;Carroll JS
通讯作者：
Carroll JS
影响因子：
64.8
作者：
Puente, Xose S.;Bea, Silvia;Campo, Elias
通讯作者：
Campo, Elias