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Involvement of Chromatin Remodeling Genes and the Rho GTPases RhoB and CDC42 in Ovarian Clear Cell Carcinoma

Authors :
Arildsen, Nicolai Skovbjerg
Jönsson, Jenny-Maria
Bartuma, Katarina
Ebbesson, Anna
Westbom-Fremer, Sofia
Måsbäck, Anna
Malander, Susanne
Nilbert, Mef
Hedenfalk, Ingrid A
Arildsen, Nicolai Skovbjerg
Jönsson, Jenny-Maria
Bartuma, Katarina
Ebbesson, Anna
Westbom-Fremer, Sofia
Måsbäck, Anna
Malander, Susanne
Nilbert, Mef
Hedenfalk, Ingrid A
Source :
Arildsen , N S , Jönsson , J-M , Bartuma , K , Ebbesson , A , Westbom-Fremer , S , Måsbäck , A , Malander , S , Nilbert , M & Hedenfalk , I A 2017 , ' Involvement of Chromatin Remodeling Genes and the Rho GTPases RhoB and CDC42 in Ovarian Clear Cell Carcinoma ' , Frontiers in Oncology , vol. 7 , 109 .
Publication Year :
2017

Abstract

OBJECTIVE: Ovarian clear cell carcinomas (OCCCs) constitute a rare ovarian cancer subtype with distinct clinical features, but may nonetheless be difficult to distinguish morphologically from other subtypes. There is limited knowledge of genetic events driving OCCC tumorigenesis beyondARID1A, which is reportedly mutated in 30-50% of OCCCs. We aimed to further characterize OCCCs by combined global transcriptional profiling and targeted deep sequencing of a panel of well-established cancer genes. Increased knowledge of OCCC-specific genetic aberrations may help in guiding development of targeted treatments and ultimately improve patient outcome.METHODS: Gene expression profiling of formalin-fixed, paraffin-embedded (FFPE) tissue from a cohort of the major ovarian cancer subtypes (cohort 1;n = 67) was performed using whole-genome cDNA-mediated Annealing, Selection, extension and Ligation (WG-DASL) bead arrays, followed by pathway, gene module score, and gene ontology analyses, respectively. A second FFPE cohort of 10 primary OCCCs was analyzed by targeted DNA sequencing of a panel of 60 cancer-related genes (cohort 2). Non-synonymous and non-sense variants affecting single-nucleotide variations and insertions or deletions were further analyzed. A tissue microarray of 43 OCCCs (cohort 3) was used for validation by immunohistochemistry and chromogenicin situhybridization.RESULTS: Gene expression analyses revealed a distinct OCCC profile compared to other histological subtypes, with, e.g.,ERBB2, TFAP2A, and genes related to cytoskeletal actin regulation being overexpressed in OCCC. ERBB2 was, however, not overexpressed on the protein level andERBB2amplification was rare in the validation cohort. Targeted deep sequencing revealed non-synonymous variants or insertions/deletions in 11/60 cancer-related genes. Genes involved in chromatin remodeling, includingARID1A, SPOP, andKMT2Dwere frequently mutated across OCCC tumors.CONCLUSION: OCCCs appear genet

Details

Database :
OAIster
Journal :
Arildsen , N S , Jönsson , J-M , Bartuma , K , Ebbesson , A , Westbom-Fremer , S , Måsbäck , A , Malander , S , Nilbert , M & Hedenfalk , I A 2017 , ' Involvement of Chromatin Remodeling Genes and the Rho GTPases RhoB and CDC42 in Ovarian Clear Cell Carcinoma ' , Frontiers in Oncology , vol. 7 , 109 .
Notes :
application/pdf, English
Publication Type :
Electronic Resource
Accession number :
edsoai.on1322708976
Document Type :
Electronic Resource