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The genomic landscape of oesophagogastric junctional adenocarcinoma.
- Source :
-
The Journal of pathology [J Pathol] 2013 Nov; Vol. 231 (3), pp. 301-10. - Publication Year :
- 2013
-
Abstract
- The incidence of oesophagogastric junctional (OGJ) adenocarcinoma is rising rapidly in western countries, in contrast to the declining frequency of distal gastric carcinoma. Treatment options for adenocarcinomas involving the oesophagogastric junction are limited and the overall prognosis is extremely poor. To determine the genomic landscape of OGJ adenocarcinoma, exomes of eight tumours and matched germline DNA were subjected to massively parallel DNA sequencing. Microsatellite instability was observed in three tumours which coincided with an elevated number of somatic mutations. In total, 117 genes were identified that had predicted coding alterations in more than one tumour. Potentially actionable coding mutations were identified in 67 of these genes, including those in CR2, HGF , FGFR4, and ESRRB. Twenty-nine genes harbouring somatic coding mutations and copy number changes in the MSS OGJ dataset are also known to be altered with similar predicted functional consequence in other tumour types. Compared with the published mutational profile of gastric cancers, 49% (57/117) of recurrently mutated genes were unique to OGJ tumours. TP53, SYNE1, and ARID1A were amongst the most frequently mutated genes in a larger OGJ cohort. Our study provides an insight into the mutational landscape of OGJ adenocarcinomas and confirms that this is a highly mutated and heterogeneous disease. Furthermore, we have uncovered somatic mutations in therapeutically relevant genes which may represent candidate drug targets.<br /> (2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.)
- Subjects :
- Adaptor Proteins, Signal Transducing analysis
Adaptor Proteins, Signal Transducing genetics
Adenocarcinoma chemistry
Adenocarcinoma pathology
Adenosine Triphosphatases analysis
Adenosine Triphosphatases genetics
Adult
Aged
DNA Copy Number Variations genetics
DNA Mutational Analysis
DNA Repair Enzymes analysis
DNA Repair Enzymes genetics
DNA-Binding Proteins analysis
DNA-Binding Proteins genetics
Esophageal Neoplasms chemistry
Esophageal Neoplasms pathology
Exome genetics
Female
Genome, Human genetics
Humans
Immunohistochemistry
Loss of Heterozygosity genetics
Male
Microsatellite Instability
Middle Aged
Mismatch Repair Endonuclease PMS2
MutL Protein Homolog 1
MutL Proteins
Neoplasm Proteins analysis
Neoplasm Proteins genetics
Neoplasm Staging
Nuclear Proteins analysis
Nuclear Proteins genetics
Polymerase Chain Reaction methods
Prospective Studies
Stomach Neoplasms chemistry
Stomach Neoplasms pathology
Adenocarcinoma genetics
DNA, Neoplasm genetics
Esophageal Neoplasms genetics
Esophagogastric Junction pathology
Mutation genetics
Stomach Neoplasms genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1096-9896
- Volume :
- 231
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- The Journal of pathology
- Publication Type :
- Academic Journal
- Accession number :
- 24308032
- Full Text :
- https://doi.org/10.1002/path.4247