Genomic aberrations in cervical adenocarcinomas in Hong Kong Chinese women

Tony K.H. Chung, Paul Van Hummelen, Paul K.S. Chan, Tak Hong Cheung, So Fan Yim, Mei Y. Yu, Matthew D. Ducar, Aaron R. Thorner, Laura E. Macconaill, Graeme Doran, Chandra Sekhar Pedamallu, Akinyemi I. Ojesina, Raymond R.Y. Wong, Vivian W. Wang, Samuel S. Freeman, Tat San Lau, Joseph Kwong, Loucia K.Y. Chan, Menachem Fromer, Taymaa MayMichael J. Worley, Katharine M. Esselen, Kevin M. Elias, Michael Lawrence, Gad Getz, David I. Smith, Christopher P. Crum, Matthew Meyerson, Ross S. Berkowitz, Yick Fu Wong

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

Although the rates of cervical squamous cell carcinoma have been declining, the rates of cervical adenocarcinoma are increasing in some countries. Outcomes for advanced cervical adenocarcinoma remain poor. Precision mapping of genetic alterations in cervical adenocarcinoma may enable better selection of therapies and deliver improved outcomes when combined with new sequencing diagnostics. We present whole-exome sequencing results from 15 cervical adenocarcinomas and paired normal samples from Hong Kong Chinese women. These data revealed a heterogeneous mutation spectrum and identified several frequently altered genes including FAT1, ARID1A, ERBB2 and PIK3CA. Exome sequencing identified human papillomavirus (HPV) sequences in 13 tumors in which the HPV genome might have integrated into and hence disrupted the functions of certain exons, raising the possibility that HPV integration can alter pathways other than p53 and pRb. Together, these provisionary data suggest the potential for individualized therapies for cervical adenocarcinoma based on genomic information. What's new? Cervical cancer is almost always associated with infections with human papilloma virus (HPV) but additional genetic mutations are required for carcinogenesis. Here the authors performed whole-exome sequencing in Hong Kong women and identified several novel recurrently mutated genes in cervical adenocarcinomas that were not present in normal adjacent tissue. Notably, HPV sequences were detected in several tumors pointing to chromosomal integration of the virus. These studies may support the development of targeted molecular therapies of cervical cancer patients in East Asia and other parts of the world.

Original languageEnglish (US)
Pages (from-to)776-783
Number of pages8
JournalInternational Journal of Cancer
Volume137
Issue number4
DOIs
StatePublished - Aug 15 2015

Keywords

  • HPV
  • cervical adenocarcinoma
  • genomic alternations

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Chung, T. K. H., Van Hummelen, P., Chan, P. K. S., Cheung, T. H., Yim, S. F., Yu, M. Y., Ducar, M. D., Thorner, A. R., Macconaill, L. E., Doran, G., Pedamallu, C. S., Ojesina, A. I., Wong, R. R. Y., Wang, V. W., Freeman, S. S., Lau, T. S., Kwong, J., Chan, L. K. Y., Fromer, M., ... Wong, Y. F. (2015). Genomic aberrations in cervical adenocarcinomas in Hong Kong Chinese women. International Journal of Cancer, 137(4), 776-783. https://doi.org/10.1002/ijc.29456