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.

Neuropilin-2 promotes tumourigenicity and metastasis in oesophageal squamous cell carcinoma through ERK-MAPK-ETV4-MMP-E-cadherin deregulation

“…Overexpression of both NRP1 and NRP2 in ESCC was confirmed (Figure A, B; see also supplementary material, Figure S1C, D). Given that NRP1 has previously been implicated in ESCC, NRP2 attracted our attention particularly since it is located on chromosome 2q, which is frequently amplified in ESCC . NRP2 protein levels were next examined by immunohistochemistry, using a tissue microarray comprising 172 cases of paired non‐tumour and primary ESCC samples.…”

“…Overexpression of oncogenes in cancers is often associated with gene copy‐number amplification. Because the NRP2 locus at chromosome 2q has been reported to be frequently amplified in ESCC , we examined whether gene amplification underlies NRP2 overexpression in ESCC. Fluorescence in situ hybridization (FISH) was carried out both on ESCC cell lines and on formalin‐fixed, paraffin‐embedded sections from 51 pairs of non‐tumour and ESCC tissue samples.…”

“…On the other hand, the role of NRP2 has not been explored in ESCC. NRP2 became an obvious candidate gene of interest, as it is located on chromosome 2q34, which has been reported to be frequently amplified in ESCC . Furthermore, NRP2 overexpression and its oncogenic properties have also been implicated in a number of tumour types, including cancers of the breast , lung , colon , pancreas , oesophagogastric tract and prostate .…”

Nkx2-8 Downregulation Promotes Angiogenesis and Activates NF-κB in Esophageal Cancer

“…Herein, we found that Nkx2-8 expression was lower at both the mRNA and protein levels in 6 of 10 cases of ESCCs, compared with the matched normal tissues. However, the Nkx2-8 gene is located in the 14q13.3 region, which is frequently amplified in ESCCs (38). Thus, it would be interesting to further investigate whether Nkx2-8 downregulation in ESCCs is associated with hypermethylation of the Nkx2-8 promoter.…”

EORTC QLQ-OES 18 module strategy for assessment of quality of life in esophageal cancer patients

“…esophageal squamous cell carcinoma (ESCC) (~90-95% of all esophageal cancer worldwide) and adenocarcinoma (EAC) (~10-15% of the total esophageal cancer cases). [2] Squamous cell cancer arises from the cells that line the upper part of the esophagus. An early indicator of this process is the increased proliferation of esophageal epithelial cells that morphologically progresses to basal cell hyperplasia, dysplasia, carcinoma in situ and invasive carcinoma.…”