Genomic imbalances in esophageal squamous cell carcinoma identified by molecular cytogenetic techniques

Abstract

This review summarizes the chromosomal changes detected by molecular cytogenetic approaches in esophageal squamous cell carcinoma (ESCC), the ninth most common malignancy in the world. Whole genome analyses of ESCC cell lines and tumors indicated that the most frequent genomic gains occurred at 1, 2q, 3q, 5p, 6p, 7, 8q, 9q, 11q, 12p, 14q, 15q, 16, 17, 18p, 19q, 20q, 22q and X, with focal amplifications at 1q32, 2p16-22, 3q25-28, 5p13-15.3, 7p12-22, 7q21-22, 8q23-24.2, 9q34, 10q21, 11p11.2, 11q13, 13q32, 14q13-14, 14q21, 14q31-32, 15q22-26, 17p11.2, 18p11.2-11.3 and 20p11.2. Recurrent losses involved 3p, 4, 5q, 6q, 7q, 8p, 9, 10p, 12p, 13, 14p, 15p, 18, 19p, 20, 22, Xp and Y. Gains at 5p and 7q, and deletions at 4p, 9p, and 11q were significant prognostic factors for patients with ESCC. Gains at 6p and 20p, and losses at 10p and 10q were the most significant imbalances, both in primary carcinoma and in metastases, which suggested that these regions may harbor oncogenes and tumor suppressor genes. Gains at 12p and losses at 3p may be associated with poor relapse-free survival. The clinical applicability of these changes as markers for the diagnosis and prognosis of ESCC, or as molecular targets for personalized therapy should be evaluated.

Keywords: CGH; FISH; esophageal carcinoma; genomic imbalances; molecular cytogenetics.

Figure 1

Summary of copy number alterations in esophageal squamous cell carcinomas (ESCC) analyzed by comparative genomic hybridization. Regions with copy number gains are represented by thin lines on the right side of the chromosome idiograms and amplifications are represented by thick bars on the same side; regions of loss are represented by thin lines on the left side of the idiograms. (A) In ESCC cell lines, the most frequent genomic gains were observed in chromosomes 1, 2q, 3q, 5p, 6p, 7, 8q, 9q, 11q, 12p, 14, 15, 16, 17, 18p, 19q, 20q, 22q and X. Focal amplifications were found at 1q32, 2p16-22, 3q25-28, 5p13-15.3, 7p12-22, 7q21-22, 8q23-24.2, 9q34, 10q21, 11p11.2, 11q13, 13q32, 14q13-14, 14q21, 14q31-32, 15q22-26, 17p11.2, 18p11.2-11.3 and 20p11.2. Recurrent losses occurred at 3p, 4, 5q, 6q, 7q, 8p, 9, 10p, 12p, 13, 14p, 15p, 18, 20, 22, Xp and Y. (B) In clinical specimens, chromosomal gains were common in 1q, 2q, 3q, 5p, 6, 7, 8q, 9, 10, 11q, 12, 13q, 14q, 16p, 17, 18q, 20 and Xq, specifically in the regions 1p34, 2p24, 2q24-34, 3q22-ter, 7p12-22, 8q13-qter, 11p11.2, 11q13, 12p11.2, 13q21-34, 17q12, 20q12-13 and Xq27-28. Recurrent losses occurred at 1p, 3q, 4p, 5q, 6, 8p, 11q, 12q, 13q, 14q, 16q, 17q, 18q, 19, 21q, 22q and Y.