Transformation of Human Fallopian Tube Stem Cells and high grade serous ovarian cancer

High-grade serous ovarian cancer (HGSOC) progresses to advanced stages without symptoms and the 5-year survival rate is a dismal 30%. Recent studies of ovaries and oviducts in patients with BRCA mutations revealed that premalignant HGSC is found almost exclusively in the fallopian tube. To validate this notion, we cloned and transformed the fallopian tube stem cells (FTSC). We demonstrated that the tumors derived from the transformed fallopian tube stem cells (FTSCt) share the similar histological and molecular feature of high-grade serous cancer. In addition, a whole-genome transcriptome analysis comparing between FTSC, immortalized fallopian tube stem cells (FTSCi), and FTSCt showing a clear molecular progression, which is mimicked by the gene expression comparison between laser captured normal oviducts and HGSOC ( cancer and paired normal samples from 10 patients). FTSCs were immortalized or transformed with retroviral infection of hTERT, SV40 and c-myc and then subcutaneously transplanted into highly immunocompromised NSG (NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ) mice. Total RNA was isolated from FTSC, immortalized FTSC, transformed FTSC, xenografting tumors. For contarol samples, we also use HGSOC and paired normal oviduct samples from 10 independent patients (samples were isolated laser captured microdissection (LCM)). We used Affymetrix chips (HG-U133_Plus_2).