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01.12.2014 | Original Article | Ausgabe 4/2014 Open Access

Familial Cancer 4/2014

Distinct gene expression profiles in ovarian cancer linked to Lynch syndrome

Zeitschrift:
Familial Cancer > Ausgabe 4/2014
Autoren:
Jenny-Maria Jönsson, Katarina Bartuma, Mev Dominguez-Valentin, Katja Harbst, Zohreh Ketabi, Susanne Malander, Mats Jönsson, Ana Carneiro, Anna Måsbäck, Göran Jönsson, Mef Nilbert
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1007/​s10689-014-9728-1) contains supplementary material, which is available to authorized users.
Jenny-Maria Jönsson and Katarina Bartuma have contributed equally to this work.

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.

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Zusatzmaterial
Supplementary material 1 (DOCX 22 kb)
10689_2014_9728_MOESM1_ESM.docx
Supplementary material 2 (TIFF 10463 kb)
10689_2014_9728_MOESM2_ESM.tif
Supplementary material 3 (TIFF 668 kb)
10689_2014_9728_MOESM3_ESM.tif
Supplementary material 4 (DOCX 42 kb)
10689_2014_9728_MOESM4_ESM.docx
Supplementary material 5 (DOCX 25 kb)
10689_2014_9728_MOESM5_ESM.docx
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