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Multisite analysis of high-grade serous epithelial ovarian cancers identifies genomic regions of focal and recurrent copy number alteration in 3q26.2 and 8q24.3.

Authors
  • Ballabio, Sara1
  • Craparotta, Ilaria1
  • Paracchini, Lara1
  • Mannarino, Laura1
  • Corso, Silvia2
  • Pezzotta, Maria Grazia3
  • Vescio, Martina1, 4
  • Fruscio, Robert5
  • Romualdi, Chiara6
  • Dainese, Emanuele3
  • Ceppi, Lorenzo5
  • Calura, Enrica6
  • Pileggi, Silvana1
  • Siravegna, Giulia7, 8
  • Pattini, Linda4
  • Martini, Paolo6
  • Delle Marchette, Martina5
  • Mangioni, Costantino2
  • Ardizzoia, Antonio3
  • Pellegrino, Antonio2
  • And 4 more
  • 1 Department of Oncology, Istituto di Ricerche Farmacologiche "Mario Negri" IRCCS, Milano, Italy. , (Italy)
  • 2 Department of Surgery, Manzoni Hospital, Lecco, Italy. , (Italy)
  • 3 Department of Oncology, Manzoni Hospital, Lecco, Italy. , (Italy)
  • 4 Department of Electronics, Information and Bioengineering, Politecnico di Milano, Milano, Italy. , (Italy)
  • 5 Clinic of Obstetrics and Gynaecology, University of Milano-Bicocca, San Gerardo Hospital, Monza, Italy. , (Italy)
  • 6 Department of Biology, University of Padova, Padova, Italy. , (Italy)
  • 7 Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Torino, Italy. , (Italy)
  • 8 Department of Oncology, University of Torino, Candiolo, Torino, Italy. , (Italy)
Type
Published Article
Journal
International Journal of Cancer
Publisher
Wiley (John Wiley & Sons)
Publication Date
Nov 15, 2019
Volume
145
Issue
10
Pages
2670–2681
Identifiers
DOI: 10.1002/ijc.32288
PMID: 30892690
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

High-grade serous epithelial ovarian cancer (HGS-EOC) is a systemic disease, with marked intra and interpatient tumor heterogeneity. The issue of spatial and temporal heterogeneity has long been overlooked, hampering the possibility to identify those genomic alterations that persist, before and after therapy, in the genome of all tumor cells across the different anatomical districts. This knowledge is the first step to clarify those molecular determinants that characterize the tumor biology of HGS-EOC and their route toward malignancy. In our study, -omics data were generated from 79 snap frozen matched tumor biopsies, withdrawn before and after chemotherapy from 24 HGS-EOC patients, gathered together from independent cohorts. The landscape of somatic copy number alterations depicts a more homogenous and stable genomic portrait than the single nucleotide variant profile. Genomic identification of significant targets in cancer analysis identified two focal and minimal common regions (FMCRs) of amplification in the cytoband 3q26.2 (region α, 193 kb long) and 8q24.3 (region β, 495 kb long). Analysis in two external databases confirmed regions α and β are features of HGS-EOC. The MECOM gene is located in region α, and 15 genes are in region β. No functional data are yet available for the genes in the β region. In conclusion, we have identified for the first time two FMCRs of amplification in HGS-EOC, opening up a potential biological role in its etiopathogenesis. © 2019 UICC.

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