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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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Public Library of Science
2011
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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. |
format | Online Article Text |
id | pubmed-3169600 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
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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