Consistent and differential genetic aberrations between esophageal dysplasia and squamous cell carcinoma detected by array comparative genomic hybridization
Menée sur 59 échantillons tumoraux prélevés lors d'une résection d'un carcinome épidermoïde de l'œsophage et sur 16 échantillons de dysplasies prélevés lors d'une biopsie, cette étude met en évidence des anomalies du nombre de copies de gènes susceptibles d'être utiles pour la détection précoce de la maladie
Purpose: Our aim was to identify frequent genomic aberrations in both ESCC and esophageal dysplasia and to discover important copy number-driving genes and microRNAs in ESCC. Experimental Design: We conducted array-based comparative genomic hybridization (array CGH) on 59 ESCC resection samples and 16 dysplasia biopsy samples. Expression of genes at 11q13.3 was analyzed by real-time PCR and immunohistochemistry (IHC). Integrated analysis was performed to identify genes or microRNAs with copy number-expression correlations. Results: Array CGH identified 11 amplifications and 8 homozygous deletions (HDs) in ESCC. Integrated analysis of array CGH data with matched gene expression microarray data showed that 90 overexpressed genes and 24 underexpressed genes were consistent with DNA copy number changes, including 12 copy number-driving microRNAs. In esophageal dysplasia, 6 gains, 4 losses, 12 amplifications and 4 homozygous deletions were detected. Amplifications of 7p11.2 and 11q13.2-11q13.3 (CCND1) and homozygous deletion at 9p21.3 (CDKN2A) were consistent genomic changes in both dysplasia and carcinoma. ANO1 at 11q13.3 was overexpressed at the mRNA and protein levels in tumors, and higher mRNA expression was correlated with the copy number increase. In particular, ANO1 expression was elevated in moderate dysplasia compared to normal esophageal epithelium. Immunohistochemistry revealed that ANO1 overexpression was positively correlated with lymph node metastasis and advanced clinical stage. Knock-down of ANO1 significantly inhibited the proliferation of KYSE30 and KYSE510 cells. Conclusion: Copy number aberrations in both esophageal dysplasia and ESCC may be useful as potential biomarkers for early detection. Additionally, ANO1 may be a candidate target gene in esophageal tumorigenesis.