High grade serous ovarian carcinomas originate in the fallopian tube.
High grade serous ovarian carcinomas originate in the fallopian tube.
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DOI：
10.1038/s41467-017-00962-1
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发表时间：
2017-10-23
影响因子：
16.6
通讯作者：
Velculescu VE
中科院分区：
文献类型：
--
作者：
Labidi-Galy SI;Papp E;Hallberg D;Niknafs N;Adleff V;Noe M;Bhattacharya R;Novak M;Jones S;Phallen J;Hruban CA;Hirsch MS;Lin DI;Schwartz L;Maire CL;Tille JC;Bowden M;Ayhan A;Wood LD;Scharpf RB;Kurman R;Wang TL;Shih IM;Karchin R;Drapkin R;Velculescu VE
高级别浆液性卵巢癌(HGSOC)是卵巢癌中最常见的类型，预后较差。有人提出，输卵管癌可能是HGSOC的先兆，但这一假说的进化证据有限。在这里，我们对激光捕获显微解剖的输卵管病变(P53信号、浆液性输卵管上皮内癌(STIC)和输卵管癌)、卵巢癌和9例患者的转移进行了全外显子序列和拷贝数分析。卵巢癌中的大多数肿瘤特异性改变出现在STIC中，包括那些影响TP53、BRCA1、BRCA2或PTEN的改变。进化分析表明，P53信号和STIC是卵巢癌的先兆，并确定从STIC的发展到卵巢癌的开始有7年的时间窗口，此后迅速转移。我们的研究结果为卵巢癌的病因研究提供了新的思路，并对卵巢癌的预防、早期发现和治疗干预具有一定的指导意义。高级别浆液性卵巢癌(HGSOC)可能起源于输卵管。在这里，作者分析了输卵管病变、卵巢癌和HGSOC患者转移的遗传变异，并建立了HGSOC在输卵管中的进化起源。
High-grade serous ovarian carcinoma (HGSOC) is the most frequent type of ovarian cancer and has a poor outcome. It has been proposed that fallopian tube cancers may be precursors of HGSOC but evolutionary evidence for this hypothesis has been limited. Here, we perform whole-exome sequence and copy number analyses of laser capture microdissected fallopian tube lesions (p53 signatures, serous tubal intraepithelial carcinomas (STICs), and fallopian tube carcinomas), ovarian cancers, and metastases from nine patients. The majority of tumor-specific alterations in ovarian cancers were present in STICs, including those affecting TP53, BRCA1, BRCA2 or PTEN. Evolutionary analyses reveal that p53 signatures and STICs are precursors of ovarian carcinoma and identify a window of 7 years between development of a STIC and initiation of ovarian carcinoma, with metastases following rapidly thereafter. Our results provide insights into the etiology of ovarian cancer and have implications for prevention, early detection and therapeutic intervention of this disease. It has previously been proposed that high-grade serous ovarian carcinoma (HGSOC) may originate from the fallopian tube. Here, the authors analyze genetic aberrances in fallopian tube lesions, ovarian cancers, and metastases from HGSOC patients and establish the evolutionary origins of HGSOC in the fallopian tube.
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影响因子：
28.2
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
通讯作者：
Lengyel E
DOI：
10.1097/pas.0b013e3181cf3d79
发表时间：
2010-03
期刊：
The American journal of surgical pathology
影响因子：
--
作者：
Kurman RJ;Shih IeM
通讯作者：
Shih IeM
影响因子：
7.3
作者：
Bashashati, Ali;Ha, Gavin;Tone, Alicia;Ding, Jiarui;Prentice, Leah M.;Roth, Andrew;Rosner, Jamie;Shumansky, Karey;Kalloger, Steve;Senz, Janine;Yang, Winnie;McConechy, Melissa;Melnyk, Nataliya;Anglesio, Michael;Luk, Margaret T. Y.;Tse, Kane;Zeng, Thomas;Moore, Richard;Zhao, Yongjun;Marra, Marco A.;Gilks, Blake;Yip, Stephen;Huntsman, David G.;McAlpine, Jessica N.;Shah, Sohrab P.
通讯作者：
Shah, Sohrab P.
影响因子：
4.7
作者：
Leeper, K;Garcia, R;Paley, P
通讯作者：
Paley, P
影响因子：
5.6
作者：
Kindelberger, David W.;Lee, Yonghee;Crum, Christopher P.
通讯作者：
Crum, Christopher P.