ID
45547
Description
Principal Investigator: Adam Bass, Dana-Farber Cancer Institute, Boston, MA; Broad Institute, Cambridge MA; Brigham and Women's Hospital, Boston, MA, USA MeSH: Esophageal Neoplasms https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000598 The incidence of esophageal adenocarcinoma (EAC) has risen 600% over the last 30 years. When coupled to the five-year survival rate of only 15% for this disease, identification of new therapeutic targets for EAC is of great importance. Here, we analyze the mutational spectra identified from the whole genome sequencing of 16 EACs and complete exome sequencing of 149 EAC tumors and matched germline samples. We identify a novel mutation signature marked by high prevalence of A to C transversions at AA*(N) trinucleotides. Notably, the development of EAC is preceded by pathologic intestinal metaplasia of the lower esophagus, Barrett's esophagus, itself a response to injury from gastric-esophageal reflux disease (GERD). Thus, we hypothesize to represent these AA*(N) mutations to a novel signature of GERD-induced mutagenesis. Analysis of the exome data identified 26 genes subject to statistically significant recurrent mutation. Of these 26 genes, only TP53, CDKN2A, SMAD4, and PIK3CA had been previously implicated in EAC. Novel mutations include those targeting chromatin modifying factors and novel candidate contributors to EAC: SPG20, TLR4, ELMO1 and DOCK2. Of these, ELMO1 and DOCK2 are notably direct dimerization partners that act to activate Rac1 to enhance cellular invasiveness, thus generating new hypotheses about the potential for the Rac1 pathway to be a novel target for therapy of EAC. "Reprinted from 'Unraveling the mutational complexity of esophageal adenocarcinoma', with permission from Nature Genetics."
Lien
https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000598
Mots-clés
Versions (1)
- 09/01/2023 09/01/2023 - Dr. med. Lucy Kessler
Détendeur de droits
Adam Bass, Dana-Farber Cancer Institute, Boston, MA; Broad Institute, Cambridge MA; Brigham and Women's Hospital, Boston, MA, USA
Téléchargé le
9 janvier 2023
DOI
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Licence
Creative Commons BY 4.0
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dbGaP phs000598 Exome Sequencing of Esophageal Adenocarcinoma
Subject ID, consent group of participants with esophageal adenocarcinoma and involved in the "Exome Sequencing of Esophageal Adenocarcinoma" project.
- StudyEvent: SEV1
- Subject ID, consent group of participants with esophageal adenocarcinoma and involved in the "Exome Sequencing of Esophageal Adenocarcinoma" project.
- Subject ID, sample ID, and sample use variable associated with participants with esophageal adenocarcinoma and involved in the "Exome Sequencing of Esophageal Adenocarcinoma" project.
- Subject ID, age, and gender of participants with esophageal adenocarcinoma and involved in the "Exome Sequencing of Esophageal Adenocarcinoma" project.
- Sample ID, sample type, analyte type, tumor status of sample, and histological type of samples obtained from participants with esophageal adenocarcinoma and involved in the "Exome Sequencing of Esophageal Adenocarcinoma" project.
Similar models
Subject ID, consent group of participants with esophageal adenocarcinoma and involved in the "Exome Sequencing of Esophageal Adenocarcinoma" project.
- StudyEvent: SEV1
- Subject ID, consent group of participants with esophageal adenocarcinoma and involved in the "Exome Sequencing of Esophageal Adenocarcinoma" project.
- Subject ID, sample ID, and sample use variable associated with participants with esophageal adenocarcinoma and involved in the "Exome Sequencing of Esophageal Adenocarcinoma" project.
- Subject ID, age, and gender of participants with esophageal adenocarcinoma and involved in the "Exome Sequencing of Esophageal Adenocarcinoma" project.
- Sample ID, sample type, analyte type, tumor status of sample, and histological type of samples obtained from participants with esophageal adenocarcinoma and involved in the "Exome Sequencing of Esophageal Adenocarcinoma" project.
C1257890 (UMLS CUI [1,2])
C0332307 (UMLS CUI [1,2])
C0332307 (UMLS CUI [1,2])
C0332307 (UMLS CUI [1,2])