大部分的人類高臨床分級(jí)漿液性上皮性卵巢癌（SEOC）常存在p53基因的突變以及RB、FOXM1途徑的異常,，部分SEOC患者存在生殖細(xì)胞或體細(xì)胞中的BRCA1/2基因突變和該基因的表觀遺傳修飾異常,，但是這些基因變化與SEOC的確切關(guān)系一直是個(gè)謎。5月23日Cancer Research 雜志在線發(fā)表了Ludmila Szabova等的研究論文闡明了其中的奧秘,。
應(yīng)用腺病毒誘導(dǎo)的Cre條件性基因失活的小鼠模型,，研究者分析了Rb、 p53 ,、Brca1 及 Brca2信號(hào)通路擾動(dòng)在上皮性卵巢癌發(fā)生和進(jìn)展中發(fā)揮的作用,。抑癌基因RB失活促使表面上皮異常增生進(jìn)展為臨床I級(jí)腫瘤。在伴有或不伴有Brca1/2基因失活的情況下,，p53雙等位基因失活或其無(wú)義突變將導(dǎo)致臨床IV級(jí)腫瘤,。與人類SEOC患者類似，在小鼠中表現(xiàn)為腹膜內(nèi)癌擴(kuò)散,、腹水以及遠(yuǎn)處轉(zhuǎn)移,。無(wú)偏性基因分析和代謝組學(xué)分析證實(shí)Rb、p53,、Brca1/2三聯(lián)突變的腫瘤與人類SEOC相對(duì)應(yīng),，而不與其他腹膜內(nèi)腫瘤對(duì)應(yīng),。
總之，該研究為分析SEOC的病因?qū)W,、治療評(píng)價(jià)和生物標(biāo)記提供了新的線索,，還有助于提高上皮性卵巢癌的成像技術(shù)。（生物谷bioon.com)
doi:10.1158/0008-5472.CAN-11-3834
Perturbation of Rb, p53 and Brca1 or Brca2 cooperate in inducing metastatic serous epithelial ovarian cancer
Ludmila Szabova, Chaoying Yin, Sujata Bupp et al.
The majority of human high grade serous epithelial ovarian cancer (SEOC) is characterized by frequent mutations in p53 and alterations in the RB and FOXM1 pathways. A subset of human SEOC harbors a combination of germline and somatic mutations as well as epigenetic dysfunction for BRCA1/2. Using Cre-conditional alleles and intrabursal induction by Cre-expressing adenovirus in genetically engineered mice, we analyzed the roles of pathway perturbations in epithelial ovarian cancer initiation and progression. Inactivation of RB-mediated tumor suppression induced surface epithelial proliferation with progression to stage I carcinoma. Additional biall elic inactivation and/or missense p53 mutation in the presence or absence of Brca1/2 caused progression to stage IV disease. As in human SEOC, mice developed peritoneal carcinomatosis, ascites, and distant metastases. Unbiased gene expression and metabolomic profiling confirmed that Rb, p53, and Brca1/2-triple mutant tumors aligned with human SEOC,and not with other intraperitoneal cancers. Together, our findings provide a novel resource for evaluating disease etiology and biomarkers, therapeutic evaluation, and improved imaging strategies in epithelial ovarian cancer.
