Molecular analysis of high-grade serous ovarian carcinoma with and without associated serous tubal intra-epithelial carcinoma

Abstract

Many high-grade serous carcinomas (HGSCs) of the pelvis are thought to originate in the distal portion of the fallopian tube. Serous tubal intra-epithelial carcinoma (STIC) lesions are the putative precursor to HGSC and identifiable in ~ 50% of advanced stage cases. To better understand the molecular etiology of HGSCs, we report a multi-center integrated genomic analysis of advanced stage tumors with and without STIC lesions and normal tissues. The most significant focal DNA SCNAs were shared between cases with and without STIC lesions. The RNA sequence and the miRNA data did not identify any clear separation between cases with and without STIC lesions. HGSCs had molecular profiles more similar to normal fallopian tube epithelium than ovarian surface epithelium or peritoneum. The data suggest that the molecular features of HGSCs with and without associated STIC lesions are mostly shared, indicating a common biologic origin, likely to be the distal fallopian tube among all cases.

Increased expression of neurotensin in high grade serous ovarian carcinoma with evidence of serous tubal intraepithelial carcinoma

“…Because molecular profiling studies in HGSC are hindered by intrapatient heterogeneity , we sought to analyze multisite tumor samples from each patient. In agreement with previous reports, we found that global expression profiles of tumors do not differentiate between HGSC‐STIC and HGSC‐NOSTIC nor is there any association between HGSC‐STIC and TCGA molecular subtypes . Moreover, our analysis suggests that tumor samples taken from multiple sites from a single patient may exhibit molecular profiles that associate with different representative TCGA molecular subtype groupings.…”

“…We speculate that the difference between this study and Ducie et al results from a combination of several factors including; utilization of tumor samples from multiple sites per patient, a more homogenous patient population (i.e. stage 3/4 only, exclusion of primary peritoneal diagnosis, single institution), and batch adjustment to combine separate analyses.…”

TET1 reprograms the epithelial ovarian cancer epigenome and reveals casein kinase 2α as a therapeutic target

“…We found that STICs displayed higher TET1 expression, compared to NFTEs (Figure A). Moreover, analysis of RNA‐seq data demonstrated higher transcript expression of TET1 in HGSOCs than in NFTE (Figure B). Likewise, immunohistochemistry showed undetectable to very low TET1 immunoreactivity in NFTE, but TET1 upregulation in HGSOCs (Figure C–F).…”

The repertoire of serous ovarian cancer non-genetic heterogeneity revealed by single-cell sequencing of normal fallopian tube epithelial cells

“…Recent studies strongly support that serous ovarian cancer can originate from the fallopian tube epithelium (FTE) with evidence from mouse models and genetic evolutionary studies (Ducie et al, 2017;Kim et al, 2012;Labidi-Galy et al, 2017;Perets et al, 2013). Previous work reported that the FTE is composed of PAX8 positive secretory, TUBB4 positive ciliated and CD44 positive basal cells (Clyman, 1966).…”