Chromosomal abnormalities and novel disease‐related regions in progression from Barrett's esophagus to esophageal adenocarcinoma
Open Access
- 18 September 2009
- journal article
- research article
- Published by Wiley in International Journal of Cancer
- Vol. 125 (10), 2349-2359
- https://doi.org/10.1002/ijc.24620
Abstract
Barrett's esophagus (BE) is a metaplastic condition caused by chronic gastroesophageal reflux which represents an early step in the development of esophageal adenocarcinoma (EAC). Single‐nucleotide polymorphism microarray (SNP‐chip) analysis is a novel, precise, high‐throughput approach to examine genomic alterations in neoplasia. Using 250K SNP‐chips, we examined the neoplastic progression of BE to EAC, studying 11 matched sample sets: 6 sets of normal esophagus (NE), BE and EAC, 4 of NE and BE and 1 of NE and EAC. Six (60%) of 10 total BE samples and 4 (57%) of 7 total EAC samples exhibited 1 or more genomic abnormalities comprising deletions, duplications, amplifications and copy‐number‐neutral loss of heterozygosity (CNN‐LOH). Several shared abnormalities were identified, including chromosome 9p CNN‐LOH [2 BE samples (20%)], deletion of CDKN2A [4 BE samples (40%)] and amplification of 17q12‐21.2 involving the ERBB2, RARA and TOP2A genes [3.1 Mb, 2 EAC (29%)]. Interestingly, 1 BE sample contained a homozygous deletion spanning 9p22.3–p22.2 (1.2 Mb): this region harbors only 1 known gene, basonuclin 2 (BNC2). Real‐time PCR analysis confirmed the deletion of this gene and decreased the expression of BNC2 mRNA in the BE sample. Furthermore, transfection and stable expression of BNC2 caused growth arrest of OE33 EAC cells, suggesting that BNC2 functions as a tumor suppressor gene in the esophagus and that deletion of this gene occurs during the development of EAC. Thus, this SNP‐chip analysis has identified several early cytogenetic events and novel candidate cancer‐related genes that are potentially involved in the evolution of BE to EAC. © 2009 UICCKeywords
This publication has 61 references indexed in Scilit:
- Frequent genomic abnormalities in acute myeloid leukemia/myelodysplastic syndrome with normal karyotypePublished by Ferrata Storti Foundation (Haematologica) ,2009
- Molecular allelokaryotyping of pediatric acute lymphoblastic leukemias by high-resolution single nucleotide polymorphism oligonucleotide genomic microarrayBlood, 2008
- Highly Sensitive Method for Genomewide Detection of Allelic Composition in Nonpaired, Primary Tumor Specimens by Use of Affymetrix Single-Nucleotide–Polymorphism Genotyping MicroarraysAmerican Journal of Human Genetics, 2007
- Genome-wide analysis of genetic alterations in acute lymphoblastic leukaemiaNature, 2007
- Basonuclins 1 and 2, whose genes share a common origin, are proteins with widely different properties and functionsProceedings of the National Academy of Sciences of the United States of America, 2006
- ERBB2 Amplifications in Esophageal AdenocarcinomaThe Annals of Thoracic Surgery, 2004
- Mutations of the BRAF gene in human cancerNature, 2002
- Molecular Biology of Barrett’s AdenocarcinomaAnnals of Surgery, 2001
- Prognostic Value of Laurén Classification and c-erbB-2 Oncogene Overexpression in Adenocarcinoma of the Esophagus and Gastroesophageal JunctionAnnals of Surgical Oncology, 1999
- Immunohistochemical detection of p53 and c-erbB-2 in oesophageal carcinoma; no correlation with prognosisEuropean Journal of Surgical Oncology, 1997