Targeted genetic and epigenetic profiling of esophageal adenocarcinomas and non-dysplastic Barrett's esophagus

Despite the efforts to describe the molecular landscape of esophageal adenocarcinoma (EAC) and its precursor lesion Barrett's esophagus (BE), discrepant findings are reported. Here, we investigated the prevalence of selected genetic (TP53 mutations and microsatellite instability (MSI) status) a...

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Bibliographic Details
Published in:Clinical epigenetics 2022-06, Vol.14 (1), p.77-77, Article 77
Main Authors: Pinto, Rita, Hauge, Tobias, Jeanmougin, Marine, Pharo, Heidi D, Kresse, Stine H, Honne, Hilde, Winge, Sara B, Five, May-Britt, Kumar, Theresa, Mala, Tom, Hauge, Truls, Johnson, Egil, Lind, Guro E
Format: Article
Language:English
Subjects:
Adenocarcinoma
Age
Analysis
Barrett's esophagus
Biopsy
Cancer therapies
DNA methylation
Epigenetic inheritance
Epigenetics
Esophageal cancer
Genes
Genetic analysis
Genetic aspects
Genetic research
Methylation
Microsatellite instability
MLH1 protein
Mutation
p53 Protein
Patients
Tissue inhibitor of metalloproteinase 3
Tumor proteins
Tumors
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Summary:Despite the efforts to describe the molecular landscape of esophageal adenocarcinoma (EAC) and its precursor lesion Barrett's esophagus (BE), discrepant findings are reported. Here, we investigated the prevalence of selected genetic (TP53 mutations and microsatellite instability (MSI) status) and epigenetic (DNA promoter hypermethylation of APC, CDKN2A, MGMT, TIMP3 and MLH1) modifications in a series of 19 non-dysplastic BE and 145 EAC samples. Additional biopsies from adjacent normal tissue were also evaluated. State-of-the-art methodologies and well-defined scoring criteria were applied in all molecular analyses. Overall, we confirmed frequent TP53 mutations among EAC (28%) in contrast to BE, which harbored no mutations. We demonstrated that MSI and MLH1 promoter hypermethylation are rare events, both in EAC and in BE. Our findings further support that APC, CDKN2A, MGMT and TIMP3 promoter hypermethylation is frequently seen in both lesions (21-89%), as well as in a subset of adjacent normal samples (up to 12%). Our study further enlightens the molecular background of BE and EAC. To the best of our knowledge, this is one of the largest studies addressing a targeted analysis of genetic and epigenetic modifications simultaneously across a combined series of non-dysplastic BE and EAC samples.
ISSN:1868-7075
1868-7083
1868-7083
1868-7075
DOI:10.1186/s13148-022-01287-7