Somatic Variations in Cervical Cancers in Indian Patients

PLoS One. 2016 Nov 9;11(11):e0165878. doi: 10.1371/journal.pone.0165878. eCollection 2016.

Abstract

There are very few reports that describe the mutational landscape of cervical cancer, one of the leading cancers in Indian women. The aim of the present study was to investigate the somatic mutations that occur in cervical cancer. Whole exome sequencing of 10 treatment naïve tumour biopsies with matched blood samples, from a cohort of Indian patients with locally advanced disease, was performed. The data revealed missense mutations across 1282 genes, out of 1831 genes harbouring somatic mutations. These missense mutations (nonsynonymous + stop-gained) when compared with pre-existing mutations in the COSMIC database showed that 272 mutations in 250 genes were already reported although from cancers other than cervical cancer. More than 1000 novel somatic variations were obtained in matched tumour samples. Pathways / genes that are frequently mutated in various other cancers were found to be mutated in cervical cancers. A significant enrichment of somatic mutations in the MAPK pathway was observed, some of which could be potentially targetable. This is the first report of whole exome sequencing of well annotated cervical cancer samples from Indian women and helps identify trends in mutation profiles that are found in an Indian cohort of cervical cancer.

MeSH terms

  • Adult
  • Carcinoma, Squamous Cell / blood
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / pathology
  • Cohort Studies
  • DNA Mutational Analysis / methods*
  • Exome / genetics*
  • Female
  • Humans
  • India
  • Middle Aged
  • Mutation Rate
  • Mutation*
  • Mutation, Missense
  • Neoplasm Staging
  • Uterine Cervical Neoplasms / blood
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / pathology

Grants and funding

The work was funded by Department of Science and Technology (DST No: SR/SO/HS-22/2009), a grant sanctioned to RM. Genotypic Technology Pvt. Ltd. and Dhitiomics Technologies Pvt. Ltd. provided support in the form of salaries/consultation fees for authors SNR and KS respectively, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. SNR provided services which included exomesequencing using Illumina platform and providing the raw data. KS, an independent consultant, was specifically brought in by Dhitiomics Technologies Pvt. Ltd., for handling the data analysis part. The specific roles of these authors are articulated in the ‘author contributions’ section.