Title
Distinct gene expression profiles in ovarian cancer linked to Lynch syndrome
Date Issued
01 December 2014
Access level
open access
Resource Type
journal article
Author(s)
Jönsson J.M.
Bartuma K.
Harbst K.
Ketabi Z.
Malander S.
Jönsson M.
Carneiro A.
Måsbäck A.
Jönsson G.
Nilbert M.
Universidad de Lund
Publisher(s)
Kluwer Academic Publishers
Abstract
Ovarian cancer linked to Lynch syndrome represents a rare subset that typically presents at young age as early-stage tumors with an overrepresentation of endometrioid and clear cell histologies. We investigated the molecular profiles of Lynch syndrome-associated and sporadic ovarian cancer with the aim to identify key discriminators and central tumorigenic mechanisms in hereditary ovarian cancer. Global gene expression profiling using whole-genome c-DNA-mediated Annealing, Selection, extension, and Ligation was applied to 48 histopathologically matched Lynch syndrome-associated and sporadic ovarian cancers. Lynch syndrome-associated and sporadic ovarian cancers differed by 349 significantly deregulated genes, including PTPRH, BIRC3, SHH and TNFRSF6B. The genes involved were predominantly linked to cell growth, proliferation, and cell-to-cell signaling and interaction. When stratified for histologic subtype, hierarchical clustering confirmed distinct differences related to heredity in the endometrioid and serous subtypes. Furthermore, separate clustering was achieved in an independent, publically available data set. The distinct genetic signatures in Lynch syndrome-associated and sporadic ovarian cancers point to alternative preferred tumorigenic routes and suggest that genetic discriminators may be relevant for molecular diagnostics and targeted therapeutics.
Start page
537
End page
545
Volume
13
Issue
4
Language
English
OCDE Knowledge area
Oncología
Patología
Subjects
Scopus EID
2-s2.0-84937512186
PubMed ID
Source
Familial Cancer
ISSN of the container
13899600
Source funding
Vetenskapsrådet
Sponsor(s)
Acknowledgments The study was conducted at the SCIBLU Genomics Facility at Lund University, Lund, Sweden. We would like to acknowledge Anna Karlsson for generous assistance with the DASL assay. Financial support was granted from a governmental funding of clinical research within the National Health Services (ALF), the Swedish Cancer Fund, the Swedish Research Council, the Nilsson Cancer Foundation and the Kamprad Cancer Foundation.
Sources of information:
Directorio de Producción Científica
Scopus