The driver mutational landscape of ovarian squamous cell carcinomas arising in mature cystic teratoma

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:Paul, Mr James and Day, Dr Elizabeth and Bell, Dr Sarah and Cooke, Dr Susanna and Evers, Ms Lisa and Ennis, Dr Darren and Biankin, Professor Andrew and Dowson, Miss Suzanne and Mcneish, Professor Iain and Martin, Ms Sancha and Glasspool, Dr Rosalind
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 > Institute 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.

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
690421Glasgow Molecular Pathology (GMP) NodeKarin OienMedical Research Council (MRC)MR/N005813/1ICS - EXPERIMENTAL THERAPEUTICS
643981Personalised biomarkers of response in high-grade serious ovarian cancerIain McNeishCancer Research UK (CRUK)C608/A15973RI CANCER SCIENCES
645511Genotype Guided Stratified Therapy for Pancreatic CancerAndrew BiankinCancer Research UK (CRUK)17263ICS - TRANSLATIONAL RESEARCH CENTRE
656911Defining Platinum and PARP Responsive Molecular Phenotypes of Pancreatic Cancer.Andrew BiankinWellcome Trust (WELLCOTR)103721/Z/14/ZICS - TRANSLATIONAL RESEARCH CENTRE
717571Developing personalised therapy for women with ovarian cancerIain McNeishBeatson Cancer Charity (BEATCANC)15-16-051RI CANCER SCIENCES
742501The Scottish Genomes PartnershipAndrew BiankinChief Scientist office (CSO)1175759/2158447ICS - TRANSLATIONAL RESEARCH CENTRE