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High Throughput Interrogation of Somatic Mutations in High Grade Serous Cancer of the Ovary

BACKGROUND: Epithelial ovarian cancer is the most lethal of all gynecologic malignancies, and high grade serous ovarian cancer (HGSC) is the most common subtype of ovarian cancer. The objective of this study was to determine the frequency and types of point somatic mutations in HGSC using a mutation...

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Autores principales: Matulonis, Ursula A., Hirsch, Michelle, Palescandolo, Emanuele, Kim, Eejung, Liu, Joyce, van Hummelen, Paul, MacConaill, Laura, Drapkin, Ronny, Hahn, William C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3169600/
https://www.ncbi.nlm.nih.gov/pubmed/21931712
http://dx.doi.org/10.1371/journal.pone.0024433
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author Matulonis, Ursula A.
Hirsch, Michelle
Palescandolo, Emanuele
Kim, Eejung
Liu, Joyce
van Hummelen, Paul
MacConaill, Laura
Drapkin, Ronny
Hahn, William C.
author_facet Matulonis, Ursula A.
Hirsch, Michelle
Palescandolo, Emanuele
Kim, Eejung
Liu, Joyce
van Hummelen, Paul
MacConaill, Laura
Drapkin, Ronny
Hahn, William C.
author_sort Matulonis, Ursula A.
collection PubMed
description BACKGROUND: Epithelial ovarian cancer is the most lethal of all gynecologic malignancies, and high grade serous ovarian cancer (HGSC) is the most common subtype of ovarian cancer. The objective of this study was to determine the frequency and types of point somatic mutations in HGSC using a mutation detection protocol called OncoMap that employs mass spectrometric-based genotyping technology. METHODOLOGY/PRINCIPAL FINDINGS: The Center for Cancer Genome Discovery (CCGD) Program at the Dana-Farber Cancer Institute (DFCI) has adapted a high-throughput genotyping platform to determine the mutation status of a large panel of known cancer genes. The mutation detection protocol, termed OncoMap has been expanded to detect more than 1000 mutations in 112 oncogenes in formalin-fixed paraffin-embedded (FFPE) tissue samples. We performed OncoMap on a set of 203 FFPE advanced staged HGSC specimens. We isolated genomic DNA from these samples, and after a battery of quality assurance tests, ran each of these samples on the OncoMap v3 platform. 56% (113/203) tumor samples harbored candidate mutations. Sixty-five samples had single mutations (32%) while the remaining samples had ≥2 mutations (24%). 196 candidate mutation calls were made in 50 genes. The most common somatic oncogene mutations were found in EGFR, KRAS, PDGRFα, KIT, and PIK3CA. Other mutations found in additional genes were found at lower frequencies (<3%). CONCLUSIONS/SIGNIFICANCE: Sequenom analysis using OncoMap on DNA extracted from FFPE ovarian cancer samples is feasible and leads to the detection of potentially druggable mutations. Screening HGSC for somatic mutations in oncogenes may lead to additional therapies for this patient population.
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spelling pubmed-31696002011-09-19 High Throughput Interrogation of Somatic Mutations in High Grade Serous Cancer of the Ovary Matulonis, Ursula A. Hirsch, Michelle Palescandolo, Emanuele Kim, Eejung Liu, Joyce van Hummelen, Paul MacConaill, Laura Drapkin, Ronny Hahn, William C. PLoS One Research Article BACKGROUND: Epithelial ovarian cancer is the most lethal of all gynecologic malignancies, and high grade serous ovarian cancer (HGSC) is the most common subtype of ovarian cancer. The objective of this study was to determine the frequency and types of point somatic mutations in HGSC using a mutation detection protocol called OncoMap that employs mass spectrometric-based genotyping technology. METHODOLOGY/PRINCIPAL FINDINGS: The Center for Cancer Genome Discovery (CCGD) Program at the Dana-Farber Cancer Institute (DFCI) has adapted a high-throughput genotyping platform to determine the mutation status of a large panel of known cancer genes. The mutation detection protocol, termed OncoMap has been expanded to detect more than 1000 mutations in 112 oncogenes in formalin-fixed paraffin-embedded (FFPE) tissue samples. We performed OncoMap on a set of 203 FFPE advanced staged HGSC specimens. We isolated genomic DNA from these samples, and after a battery of quality assurance tests, ran each of these samples on the OncoMap v3 platform. 56% (113/203) tumor samples harbored candidate mutations. Sixty-five samples had single mutations (32%) while the remaining samples had ≥2 mutations (24%). 196 candidate mutation calls were made in 50 genes. The most common somatic oncogene mutations were found in EGFR, KRAS, PDGRFα, KIT, and PIK3CA. Other mutations found in additional genes were found at lower frequencies (<3%). CONCLUSIONS/SIGNIFICANCE: Sequenom analysis using OncoMap on DNA extracted from FFPE ovarian cancer samples is feasible and leads to the detection of potentially druggable mutations. Screening HGSC for somatic mutations in oncogenes may lead to additional therapies for this patient population. Public Library of Science 2011-09-08 /pmc/articles/PMC3169600/ /pubmed/21931712 http://dx.doi.org/10.1371/journal.pone.0024433 Text en Matulonis et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Matulonis, Ursula A.
Hirsch, Michelle
Palescandolo, Emanuele
Kim, Eejung
Liu, Joyce
van Hummelen, Paul
MacConaill, Laura
Drapkin, Ronny
Hahn, William C.
High Throughput Interrogation of Somatic Mutations in High Grade Serous Cancer of the Ovary
title High Throughput Interrogation of Somatic Mutations in High Grade Serous Cancer of the Ovary
title_full High Throughput Interrogation of Somatic Mutations in High Grade Serous Cancer of the Ovary
title_fullStr High Throughput Interrogation of Somatic Mutations in High Grade Serous Cancer of the Ovary
title_full_unstemmed High Throughput Interrogation of Somatic Mutations in High Grade Serous Cancer of the Ovary
title_short High Throughput Interrogation of Somatic Mutations in High Grade Serous Cancer of the Ovary
title_sort high throughput interrogation of somatic mutations in high grade serous cancer of the ovary
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3169600/
https://www.ncbi.nlm.nih.gov/pubmed/21931712
http://dx.doi.org/10.1371/journal.pone.0024433
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