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Study Description

Cervical cancer is responsible for 10-15% of cancer related deaths in women worldwide. The etiological role of infection with high-risk human papilloma viruses (HPV) in carcinomas of the cervix is well established. In general, the development of cervical carcinomas follows a progression from persistent HPV infection through precancerous lesions to invasive cancer. Previous studies have implicated somatic mutations in PIK3CA, PTEN, TP53, STK11 and KRAS as well as chromosome-arm level copy number alterations in the pathogenesis of cervical carcinomas. Here, we report whole exome sequencing analysis of 118 cervical carcinoma-normal paired samples from patients in Norway and Mexico, as well as transcriptome sequencing of 80 cases and whole genome sequencing of 13 tumor-normal pairs. Novel somatic mutations include recurrent E322K substitutions in the MAPK1 gene encoding the ERK2 kinase and inactivating mutations in the HLA-B gene. In addition, recurrent somatic mutations in FBXW7, EP300, and NFE2L2 are novel in the context of primary cervical carcinomas. Analysis of HPV integration sites revealed recurrent integration into the RAD51B locus as well as co-occurrence of HPV genome integration and copy number gains within several genomic loci. These findings shed new light on the pathogenesis of cervical carcinomas and suggest potential novel therapeutic targets.

  • Study Type: Case-Control
  • Number of study subjects that have individual level data available through Authorized Access: 115

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Study Inclusion/Exclusion Criteria

Surgically resected tumors or biopsies were freshly frozen in nitrogen and stored at minus 800C. Genomic DNA and RNA were extracted from tumors found to have > 40-50% malignant epithelial component based on assessment of hematoxylin stained frozen sections. The Norwegian sample set was enriched for stage IB surgically resectable, grade III tumors. Hematoxylin-eosin slides were reviewed by a pathologist for determination of diagnosis and histological subtype and tumor purity. DNA was also extracted from peripheral blood as corresponding normal. DNA quality was assessed by Affymetrix SNP 6.0 arrays and SNP comparison was used to confirm that a sequenced tumor-normal pair could be attributed to the same individual and that no significant contamination by foreign DNA was present.

Molecular Data
TypeSourcePlatformNumber of Oligos/SNPsSNP Batch IdComment
Whole Genome Sequencing Illumina HiSeq 2000 N/A N/A
Whole Exome Sequencing Illumina HiSeq 2000 N/A N/A
Study History

Samples were prospectively collected

  1. Norwegian samples: May 2001- May 2011
  2. Mexican samples: May 2011 - August 2011

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Diseases/Traits Related to Study (MESH terms)
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Study Attribution