The genomic landscape and evolution of endometrial carcinoma progression and abdominopelvic metastasis.
The genomic landscape and evolution of endometrial carcinoma progression and abdominopelvic metastasis.
复制标题
DOI：
10.1038/ng.3602
复制
发表时间：
2016-08
期刊：
影响因子：
30.8
通讯作者：
Salvesen HB
中科院分区：
文献类型：
--
作者：
Gibson WJ;Hoivik EA;Halle MK;Taylor-Weiner A;Cherniack AD;Berg A;Holst F;Zack TI;Werner HM;Staby KM;Rosenberg M;Stefansson IM;Kusonmano K;Chevalier A;Mauland KK;Trovik J;Krakstad C;Giannakis M;Hodis E;Woie K;Bjorge L;Vintermyr OK;Wala JA;Lawrence MS;Getz G;Carter SL;Beroukhim R;Salvesen HB
最近的研究已经详细描述了原发性子宫内膜癌的基因组图景，但其演变为转移的特征尚未确定。我们对98例肿瘤活检标本进行了全外显子测序，包括复杂的不典型增生、原发肿瘤和配对的腹盆腔转移瘤，以调查子宫内膜癌的进化图景。我们扩展和重新分析了TCGA数据，确定了原发肿瘤中新的复发改变，包括12%的患者中雌激素受体辅助因子NRIP1的突变。我们发现，可能的驱动事件倾向于在原发和转移组织样本中共享，但显著的例外情况如ARID1A突变。系统发育分析表明，抽样的转移瘤通常来自一个共同的祖先亚克隆，而初级肿瘤活检中没有检测到这种亚克隆。这些数据显示子宫内膜癌中广泛的遗传异质性和转移部位的相对同质性。
Recent studies have detailed the genomic landscape of primary endometrial cancers, but their evolution into metastases has not been characterized. We performed whole-exome sequencing of 98 tumor biopsies including complex atypical hyperplasias, primary tumors, and paired abdominopelvic metastases to survey the evolutionary landscape of endometrial cancer. We expanded and reanalyzed TCGA-data, identifying novel recurrent alterations in primary tumors, including mutations in the estrogen receptor cofactor NRIP1 in 12% of patients. We found that likely driver events tended to be shared by primary and metastatic tissue-samples, with notable exceptions such as ARID1A mutations. Phylogenetic analyses indicated that the sampled metastases typically arose from a common ancestral subclone that was not detected in the primary tumor biopsy. These data demonstrate extensive genetic heterogeneity within endometrial cancers and relative homogeneity across metastatic sites.