Pre-invasive ovarian mucinous tumors are characterized by CDKN2A and RAS pathway aberrations.

Content Provider	Semantic Scholar
Author	Hunter, Sally M. Gorringe, Kylie L. Christie, Michael John Rowley, Simone M. Bowtell, David D. L. Campbell, Ian G.
Copyright Year	2012
Abstract	INTRODUCTION Mucinous tumors are the second most common form of epithelial ovarian tumor, yet the cell of origin for this histologic subtype remains undetermined. Although these tumors are thought to arise through a stepwise progression from benign cystadenoma to borderline tumor to invasive carcinoma, few studies have attempted to comprehensively characterize the genetic changes specific to this subtype or its precursors. METHODS To explore the spectrum of genomic alterations common to mucinous tumors we carried out high-resolution genome-wide copy number analysis, mutation screening by Sanger sequencing and immunohistochemistry on a series of primary ovarian mucinous cystadenomas (n = 20) and borderline tumors (n = 22). RESULTS Integration of copy number data, targeted mutation screening of RAS/RAF pathway members and immunohistochemistry reveals that p16 loss and RAS/RAF pathway alterations are highly recurrent events that occur early during mucinous tumor development. The frequency of concurrence of these events was observed in 40% of benign cystadenomas and 68% of borderline tumors. CONCLUSIONS This study is the largest and highest resolution analysis of mucinous benign and borderline tumors carried out to date and provides strong support for these lesions being precursors of primary ovarian mucinous adenocarcinoma. The high level of uniformity in the molecular events underlying the pathogenesis of mucinous ovarian tumors provides an opportunity for treatments targeting specific mutations and pathways.
Starting Page	404
Ending Page	408
Page Count	5
File Format	PDF HTM / HTML
Alternate Webpage(s)	http://clincancerres.aacrjournals.org/content/clincanres/early/2012/09/16/1078-0432.CCR-12-1103.full.pdf
Alternate Webpage(s)	http://clincancerres.aacrjournals.org/content/clincanres/early/2012/08/11/1078-0432.CCR-12-1103.full.pdf
PubMed reference number	22891197v1
Alternate Webpage(s)	https://doi.org/10.1158/1078-0432.CCR-12-1103
DOI	10.1158/1078-0432.ccr-12-1103
Journal	Clinical cancer research : an official journal of the American Association for Cancer Research
Volume Number	18
Issue Number	19
Language	English
Access Restriction	Open
Subject Keyword	Attempt Biomarkers, Tumor Biopolymer Sequencing Copy Number Cyclin-Dependent Kinase Inhibitor 2A, human Cystadenoma Cystadenoma, Mucinous Invasive Carcinoma Mutation Neoplasms Neoplasms, Unknown Primary Ovarian Mucinous Adenocarcinoma Ovarian Mucinous Tumor Pineal Gland Neoplasm neoplasm of uncertain malignant potential ovarian neoplasm
Content Type	Text
Resource Type	Article