Genomics of Ovarian Cancer Progression Reveals Diverse Metastatic Trajectories Including Intraepithelial Metastasis to the Fallopian Tube.
Genomics of Ovarian Cancer Progression Reveals Diverse Metastatic Trajectories Including Intraepithelial Metastasis to the Fallopian Tube.
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DOI：
10.1158/2159-8290.cd-16-0607
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发表时间：
2016-12
期刊：
影响因子：
28.2
通讯作者：
Lengyel E
中科院分区：
文献类型：
--
作者：
Eckert MA;Pan S;Hernandez KM;Loth RM;Andrade J;Volchenboum SL;Faber P;Montag A;Lastra R;Peter ME;Yamada SD;Lengyel E
越来越多的证据支持输卵管而不是卵巢作为高级别浆液性卵巢癌（HGSOC）的起源。为了了解假定的前体病变和转移性肿瘤之间的关系，我们对八个 HGSOC 患者进展系列的标本进行了全外显子组测序，其中包括浆液性输卵管上皮内癌 (STIC)、侵袭性输卵管病变、侵袭性卵巢病变和大网膜转移瘤。拷贝数和体细胞突变的整合揭示了所有解剖位点具有相似突变特征和拷贝数变异谱的患者特异性模式，表明基因组不稳定是 HGSOC 的早期事件。系统发育分析支持 STIC 是我们一半患者队列中的前驱病变，但也确定 STIC 是两名患者的转移灶。离体测定表明 HGSOC 球体可以植入输卵管上皮并模拟 STIC 病变。 STIC 可能代表转移，这对 STIC 始终指示原发性输卵管癌的假设提出了质疑。
Accumulating evidence has supported the fallopian tube rather than the ovary as the origin for high grade serous ovarian cancer (HGSOC). To understand the relationship between putative precursor lesions and metastatic tumors, we performed whole exome sequencing on specimens from eight HGSOC patient progression series consisting of serous tubal intraepithelial carcinomas (STIC), invasive fallopian tube lesions, invasive ovarian lesions, and omental metastases. Integration of copy number and somatic mutations revealed patient-specific patterns with similar mutational signatures and copy number variation profiles across all anatomic sites, suggesting that genomic instability is an early event in HGSOC. Phylogenetic analyses supported STIC as precursor lesions in half of our patient cohort, but also identified STIC as metastases in two patients. Ex vivo assays revealed that HGSOC spheroids can implant in the fallopian tube epithelium and mimic STIC lesions. That STIC may represent metastases calls into question the assumption that STIC are always indicative of primary fallopian tube cancers.