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Focal Recurrent Copy Number Alterations Characterize Disease Relapse in High Grade Serous Ovarian Cancer Patients with Good Clinical Prognosis: A Pilot Study

High grade serous ovarian cancer (HGSOC) retains high molecular heterogeneity and genomic instability, which currently limit the treatment opportunities. HGSOC patients receiving complete cytoreduction (R0) at primary surgery and platinum-based therapy may unevenly experience early disease relapse,...

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Autores principales: Dugo, Matteo, Devecchi, Andrea, De Cecco, Loris, Cecchin, Erika, Mezzanzanica, Delia, Sensi, Marialuisa, Bagnoli, Marina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6770978/
https://www.ncbi.nlm.nih.gov/pubmed/31491988
http://dx.doi.org/10.3390/genes10090678
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author Dugo, Matteo
Devecchi, Andrea
De Cecco, Loris
Cecchin, Erika
Mezzanzanica, Delia
Sensi, Marialuisa
Bagnoli, Marina
author_facet Dugo, Matteo
Devecchi, Andrea
De Cecco, Loris
Cecchin, Erika
Mezzanzanica, Delia
Sensi, Marialuisa
Bagnoli, Marina
author_sort Dugo, Matteo
collection PubMed
description High grade serous ovarian cancer (HGSOC) retains high molecular heterogeneity and genomic instability, which currently limit the treatment opportunities. HGSOC patients receiving complete cytoreduction (R0) at primary surgery and platinum-based therapy may unevenly experience early disease relapse, in spite of their clinically favorable prognosis. To identify distinctive traits of the genomic landscape guiding tumor progression, we focused on the R0 patients of The Cancer Genome Atlas (TCGA) ovarian serous cystadenocarcinoma (TCGA-OV) dataset and classified them according to their time to relapse (TTR) from surgery. We included in the study two groups of R0-TCGA patients experiencing substantially different outcome: Resistant (R; TTR ≤ 12 months; n = 11) and frankly Sensitive (fS; TTR ≥ 24 months; n = 16). We performed an integrated clinical, RNA-Sequencing, exome and somatic copy number alteration (sCNA) data analysis. No significant differences in mutational landscape were detected, although the lack of BRCA-related mutational signature characterized the R group. Focal sCNA analysis showed a higher frequency of amplification in R group and deletions in fS group respectively, involving cytobands not commonly detected by recurrent sCNA analysis. Functional analysis of focal sCNA with a concordantly altered gene expression identified in R group a gain in Notch, and interferon signaling and fatty acid metabolism. We are aware of the constraints related to the low number of OC cases analyzed. It is worth noting, however, that the sCNA identified in this exploratory analysis and characterizing Pt-resistance are novel, deserving validation in a wider cohort of patients achieving complete surgical debulking.
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spelling pubmed-67709782019-10-30 Focal Recurrent Copy Number Alterations Characterize Disease Relapse in High Grade Serous Ovarian Cancer Patients with Good Clinical Prognosis: A Pilot Study Dugo, Matteo Devecchi, Andrea De Cecco, Loris Cecchin, Erika Mezzanzanica, Delia Sensi, Marialuisa Bagnoli, Marina Genes (Basel) Article High grade serous ovarian cancer (HGSOC) retains high molecular heterogeneity and genomic instability, which currently limit the treatment opportunities. HGSOC patients receiving complete cytoreduction (R0) at primary surgery and platinum-based therapy may unevenly experience early disease relapse, in spite of their clinically favorable prognosis. To identify distinctive traits of the genomic landscape guiding tumor progression, we focused on the R0 patients of The Cancer Genome Atlas (TCGA) ovarian serous cystadenocarcinoma (TCGA-OV) dataset and classified them according to their time to relapse (TTR) from surgery. We included in the study two groups of R0-TCGA patients experiencing substantially different outcome: Resistant (R; TTR ≤ 12 months; n = 11) and frankly Sensitive (fS; TTR ≥ 24 months; n = 16). We performed an integrated clinical, RNA-Sequencing, exome and somatic copy number alteration (sCNA) data analysis. No significant differences in mutational landscape were detected, although the lack of BRCA-related mutational signature characterized the R group. Focal sCNA analysis showed a higher frequency of amplification in R group and deletions in fS group respectively, involving cytobands not commonly detected by recurrent sCNA analysis. Functional analysis of focal sCNA with a concordantly altered gene expression identified in R group a gain in Notch, and interferon signaling and fatty acid metabolism. We are aware of the constraints related to the low number of OC cases analyzed. It is worth noting, however, that the sCNA identified in this exploratory analysis and characterizing Pt-resistance are novel, deserving validation in a wider cohort of patients achieving complete surgical debulking. MDPI 2019-09-05 /pmc/articles/PMC6770978/ /pubmed/31491988 http://dx.doi.org/10.3390/genes10090678 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Dugo, Matteo
Devecchi, Andrea
De Cecco, Loris
Cecchin, Erika
Mezzanzanica, Delia
Sensi, Marialuisa
Bagnoli, Marina
Focal Recurrent Copy Number Alterations Characterize Disease Relapse in High Grade Serous Ovarian Cancer Patients with Good Clinical Prognosis: A Pilot Study
title Focal Recurrent Copy Number Alterations Characterize Disease Relapse in High Grade Serous Ovarian Cancer Patients with Good Clinical Prognosis: A Pilot Study
title_full Focal Recurrent Copy Number Alterations Characterize Disease Relapse in High Grade Serous Ovarian Cancer Patients with Good Clinical Prognosis: A Pilot Study
title_fullStr Focal Recurrent Copy Number Alterations Characterize Disease Relapse in High Grade Serous Ovarian Cancer Patients with Good Clinical Prognosis: A Pilot Study
title_full_unstemmed Focal Recurrent Copy Number Alterations Characterize Disease Relapse in High Grade Serous Ovarian Cancer Patients with Good Clinical Prognosis: A Pilot Study
title_short Focal Recurrent Copy Number Alterations Characterize Disease Relapse in High Grade Serous Ovarian Cancer Patients with Good Clinical Prognosis: A Pilot Study
title_sort focal recurrent copy number alterations characterize disease relapse in high grade serous ovarian cancer patients with good clinical prognosis: a pilot study
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6770978/
https://www.ncbi.nlm.nih.gov/pubmed/31491988
http://dx.doi.org/10.3390/genes10090678
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