论文标题：The prognostic effects of somatic mutations in ER-positive breast cancer
期刊：
作者：Elaine R Mardis & Matthew J. Ellis et al
发表时间：2018/09/04
数字识别码：10.1038/s41467-018-05914-x
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《自然-通讯》发表的一项研究The prognostic effects of somatic mutations in ER-positive breast cancer指出，雌激素受体阳性乳腺癌患者体内三种罕见的基因突变会对疾病的预后产生不良影响。
图1：突变复发和新的剪接位点突变。图源：Griffith et al.
雌激素受体阳性乳腺癌的结局差异显著，而罕见的基因突变对该病预后的影响仍不甚明确。众所周知，DNA突变会促使细胞生物学性状发生改变，并导致癌症。但要弄清罕见的基因突变与疾病结局之间的关系颇有难度。为了确定罕见的基因突变与雌激素受体阳性乳腺癌之间的关系，需要使用长期临床随访数据和遗传信息。
美国贝勒明升手机版院的Matthew Ellis及同事对三组绝经后（625位）和绝经前（328位）的雌激素受体阳性乳腺癌患者的DNA信息进行了研究。通过存档的甲醛固定的石蜡包埋组织以及对83个基因的靶向测序，作者发现雌激素受体阳性乳腺癌患者较差的临床结局与NF1、PIK3R1和DDR1这三个基因的突变有关。
图2：交叉队列的年龄和肿瘤亚型分析。图源：Griffith et al.
该研究证实，罕见频发的基因突变会影响预后，这一发现或有助于解释雌激素受体阳性乳腺癌患者的结局差异显著的原因。
摘要：Here we report targeted sequencing of 83 genes using DNA from primary breast cancer samples from 625 postmenopausal (UBC-TAM series) and 328 premenopausal (MA12 trial) hormone receptor-positive (HR+) patients to determine interactions between somatic mutation and prognosis. Independent validation of prognostic interactions was achieved using data from the METABRIC study. Previously established associations between MAP3K1 and PIK3CA mutations with luminal A status/favorable prognosis and TP53 mutations with Luminal B/non-luminal tumors/poor prognosis were observed, validating the methodological approach. In UBC-TAM, NF1 frame-shift nonsense (FS/NS) mutations were also a poor outcome driver that was validated in METABRIC. For MA12, poor outcome associated with PIK3R1 mutation was also reproducible. DDR1 mutations were strongly associated with poor prognosis in UBC-TAM despite stringent false discovery correction (q = 0.0003). In conclusion, uncommon recurrent somatic mutations should be further explored to create a more complete explanation of the highly variable outcomes that typifies ER+ breast cancer.
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