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...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2011-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3169600?pdf=render |
| _version_ | 1818278798615904256 |
|---|---|
| author | Ursula A Matulonis Michelle Hirsch Emanuele Palescandolo Eejung Kim Joyce Liu Paul van Hummelen Laura MacConaill Ronny Drapkin William C Hahn |
| author_facet | Ursula A Matulonis Michelle Hirsch Emanuele Palescandolo Eejung Kim Joyce Liu Paul van Hummelen Laura MacConaill Ronny Drapkin William C Hahn |
| author_sort | Ursula A Matulonis |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-12T23:23:10Z |
| format | Article |
| id | doaj.art-8e51a7e43ef44f39b5c050d57843a018 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-12T23:23:10Z |
| publishDate | 2011-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-8e51a7e43ef44f39b5c050d57843a0182022-12-22T00:08:13ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-0169e2443310.1371/journal.pone.0024433High throughput interrogation of somatic mutations in high grade serous cancer of the ovary.Ursula A MatulonisMichelle HirschEmanuele PalescandoloEejung KimJoyce LiuPaul van HummelenLaura MacConaillRonny DrapkinWilliam C HahnBACKGROUND: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.http://europepmc.org/articles/PMC3169600?pdf=render |
| spellingShingle | Ursula A Matulonis Michelle Hirsch Emanuele Palescandolo Eejung Kim Joyce Liu Paul van Hummelen Laura MacConaill Ronny Drapkin William C Hahn High throughput interrogation of somatic mutations in high grade serous cancer of the ovary. PLoS ONE |
| 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 |
| url | http://europepmc.org/articles/PMC3169600?pdf=render |
| work_keys_str_mv | AT ursulaamatulonis highthroughputinterrogationofsomaticmutationsinhighgradeserouscanceroftheovary AT michellehirsch highthroughputinterrogationofsomaticmutationsinhighgradeserouscanceroftheovary AT emanuelepalescandolo highthroughputinterrogationofsomaticmutationsinhighgradeserouscanceroftheovary AT eejungkim highthroughputinterrogationofsomaticmutationsinhighgradeserouscanceroftheovary AT joyceliu highthroughputinterrogationofsomaticmutationsinhighgradeserouscanceroftheovary AT paulvanhummelen highthroughputinterrogationofsomaticmutationsinhighgradeserouscanceroftheovary AT lauramacconaill highthroughputinterrogationofsomaticmutationsinhighgradeserouscanceroftheovary AT ronnydrapkin highthroughputinterrogationofsomaticmutationsinhighgradeserouscanceroftheovary AT williamchahn highthroughputinterrogationofsomaticmutationsinhighgradeserouscanceroftheovary |