ID

45548

Description

Principal Investigator: Matthew Meyerson, MD,PhD, Dana Farber Cancer Institute, Boston MA, USA MeSH: Uterine Cervical Neoplasms https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000600 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.

Lien

https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000600

Mots-clés

  1. 09/01/2023 09/01/2023 - Dr. med. Lucy Kessler
Détendeur de droits

Matthew Meyerson, MD,PhD, Dana Farber Cancer Institute, Boston MA, USA

Téléchargé le

9 janvier 2023

DOI

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Licence

Creative Commons BY 4.0

Modèle Commentaires :

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dbGaP phs000600 Genomic Sequencing of Cervical Cancers

Eligibility Criteria

Inclusion and exclusion criteria
Description

Inclusion and exclusion criteria

Alias
UMLS CUI [1,1]
C1512693
UMLS CUI [1,2]
C0680251
Surgically resected tumors or biopsies were freshly frozen in nitrogen and stored at minus 80<sup>0</sup>C. Genomic DNA and RNA were extracted from tumors found to have &#62; 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.
Description

Elig.phs000600.v1.p1.1

Type de données

boolean

Alias
UMLS CUI [1,1]
C3846158

Similar models

Eligibility Criteria

Name
Type
Description | Question | Decode (Coded Value)
Type de données
Alias
Item Group
Inclusion and exclusion criteria
C1512693 (UMLS CUI [1,1])
C0680251 (UMLS CUI [1,2])
Elig.phs000600.v1.p1.1
Item
Surgically resected tumors or biopsies were freshly frozen in nitrogen and stored at minus 80<sup>0</sup>C. Genomic DNA and RNA were extracted from tumors found to have &#62; 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.
boolean
C3846158 (UMLS CUI [1,1])

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