Chromosome arm 20q gains and other genomic alterations in esophageal squamous cell carcinoma, as analyzed by comparative genomic hybridization and fluorescence in situ hybridization.

ABSTRACT

BACKGROUND/AIMS: Our recent analysis of gastric cancers and colorectal cancers using comparative genomic hybridization revealed a novel, high frequent copy number increases the long arm of chromosome 20 in association with possible involvement of liver metastases and poor prognosis. This led to further comparative genomic hybridization analysis of chromosomal aberrations in primary tumors of esophageal squamous cell carcinoma. The aim of the study presented here was to analyze the chromosomal aberrations and to determine the numbers of copies of AIB1, BTAK, DcR3 and E2F1 as putative target genes on chromosome 20q as well as their expression and relation to clinicopathological features in 41 primary tumors of esophageal squamous cell carcinoma. METHODOLOGY: We used comparative genomic hybridization to screen 41 primary tumors of esophageal squamous cell carcinoma for changes in the number of copies of DNA sequences. To further characterize the gain of DNA sequences at 20q, we also performed fluorescence in situ hybridization analysis. We examined the relationship between these changes and clinicopathological factors. RESULTS: Gains in chromosome arm 20q were detected (34.1%) as well as a high level of gain in 20q12-13 (4.8%). AIB1 amplification was observed in 4.9% (2/41), BTAK amplification in 9.8% (4/41), DcR3 amplification was in 4.9% (2/41), and E2F1 amplification in 7.3% (3/41). The survival of patients with BTAK or E2F1 amplification was significantly lower than that of patients without these abnormalities. CONCLUSIONS: These findings provide evidence for a number of previously unknown genomic aberrations in esophageal squamous cell carcinoma, suggesting the existence of target regions relevant to its progression. Esophageal squamous cell carcinoma with 20q gain showed extensive lung metastases, pleural effusion and liver metastases and poorer prognosis compared to cases without 20q gain. Our results suggest that amplification of BTAK or E2F1 are likely to lead to an increase in the number of malignant phenotypes of esophageal squamous cell carcinoma and that these aberrations can be expected to be useful as markers of poor prognosis.