The driver mutational landscape of ovarian squamous cell carcinomas arising in mature cystic teratoma (original) (raw)
Cooke, S. L. et al. (2017) The driver mutational landscape of ovarian squamous cell carcinomas arising in mature cystic teratoma.Clinical Cancer Research, 23(24), pp. 7633-7640. (doi: 10.1158/1078-0432.CCR-17-1789) (PMID:28954785)
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Abstract
Purpose. We sought to identify the genomic abnormalities in squamous cell carcinomas (SCC) arising in ovarian mature cystic teratoma (MCT), a rare gynaecological malignancy of poor prognosis. Experimental design. We performed copy number, mutational state and zygosity analysis of 151 genes in SCC arising in MCT (n=25) using next-generation sequencing. The presence of high/intermediate risk HPV genotypes was assessed by quantitative PCR. Genomic events were correlated with clinical features and outcome Results. MCT had a low mutation burden with a mean of only 1 mutation per case. Zygosity analyses of MCT indicated four separate patterns, suggesting that MCT can arise from errors at various stages of oogenesis. A total of 244 abnormalities were identified in 79 genes in MCT-associated SCC, and the overall mutational burden was high (mean 10.2 mutations per megabase). No SCC was positive for HPV. The most frequently altered genes in SCC were TP53 (20/25 cases, 80%), PIK3CA (13/25 cases, 52%) and CDKN2A (11/25 cases, 44%). Mutation in TP53 was associated with improved overall survival. In 8/20 cases with TP53 mutations, two or more variants were identified, which were bi-allelic. Conclusions. Ovarian SCC arising in MCT has a high mutational burden with TP53 mutation the most common abnormality. The presence TP53 mutation is a good prognostic factor. SCC arising in MCT share similar mutation profiles to other SCC. Given their rarity, they should be included in basket studies that recruit patients with SCC of other organs.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Dowson, Miss Suzanne and Ennis, Dr Darren and Paul, Mr James and Biankin, Professor Andrew and Mcneish, Professor Iain and Day, Dr Elizabeth and Martin, Ms Sancha and Cooke, Dr Susie and Evers, Ms Lisa and Glasspool, Dr Rosalind and Bell, Dr Sarah |
| Authors: | Cooke, S. L., Ennis, D., Evers, L., Dowson, S., Chan, M. Y., Paul, J., Hirschowitz, L., Glasspool, R., Singh, N., Bell, S., Day, E. K., Kochman, A., Wilkinson, N., Beer, P., Martin, S., Millan, D. W., Biankin, A. V., and McNeish, I. A. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Cancer Sciences |
| Journal Name: | Clinical Cancer Research |
| Publisher: | American Association for Cancer Research |
| ISSN: | 1078-0432 |
| ISSN (Online): | 1557-3265 |
| Published Online: | 27 September 2017 |
| Copyright Holders: | Copyright © 2017 American Association for Cancer Research |
| First Published: | First published in Clinical Cancer Research 23(24):7633-7640 |
| Publisher Policy: | Reproduced in accordance with the copyright policy of the publisher. |
University Staff: Request a correction | Enlighten Editors: Update this record
Funder and Project Information
1
Glasgow Molecular Pathology (GMP) Node
Karin Oien
MR/N005813/1
ICS - EXPERIMENTAL THERAPEUTICS
1
Personalised biomarkers of response in high-grade serious ovarian cancer
Iain McNeish
C608/A15973
RI CANCER SCIENCES
1
Genotype Guided Stratified Therapy for Pancreatic Cancer
Andrew Biankin
17263
ICS - TRANSLATIONAL RESEARCH CENTRE
1
Defining Platinum and PARP Responsive Molecular Phenotypes of Pancreatic Cancer.
Andrew Biankin
103721/Z/14/Z
ICS - TRANSLATIONAL RESEARCH CENTRE
1
Developing personalised therapy for women with ovarian cancer
Iain McNeish
15-16-051
RI CANCER SCIENCES
1
The Scottish Genomes Partnership
Andrew Biankin
1175759/2158447
ICS - TRANSLATIONAL RESEARCH CENTRE
Deposit and Record Details
| ID Code: | 148750 |
|---|---|
| Depositing User: | Ms Mary Anne Meyering |
| Datestamp: | 25 Sep 2017 08:54 |
| Last Modified: | 02 May 2025 15:22 |
| Date of acceptance: | 22 September 2017 |
| Date of first online publication: | 27 September 2017 |
| Date Deposited: | 25 September 2017 |
| Data Availability Statement: | No |