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 |
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Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Day, Dr Elizabeth and Bell, Dr Sarah and Cooke, Dr Susie and Biankin, Professor Andrew and Dowson, Miss Suzanne and Martin, Ms Sancha and Glasspool, Dr Rosalind and Paul, Mr James and Evers, Ms Lisa and Ennis, Dr Darren and Mcneish, Professor Iain |
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. |
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