Abstract 3050: Detection of recurrent genomic alterations using array-CGH and high resolution-CGH in esophageal squamous cell carcinoma (ESCC)

Esophageal squamous cell carcinoma (ESCC) is the 8th most common cancer worldwide and the 6th tumor in frequency in Brazil. Most of cases are diagnosed at an advanced stage and despite the improvement of various treatment modalities the overall survival rates still remain low. The aim of this study was to identify the recurrent genomic alterations in ESCC using comparative genomic hybridization (CGH) and to correlate these findings with clinicopathological data. High resolution-comparative genomic hybridization (HR-CGH) was performed in 21 FFPE tissue samples. Array-CGH (aCGH) was carried out in 18 frozen tissue samples using the Agilent Human Genome CGH Microarray 44K following the manufacturer9s protocol. Data were extracted and flagged with Feature Extraction (version 10.1.1.1), processed using Genomic Workbench Standard (version.5.0.14), with the statistical algorithm ADM-2 and sensitivity threshold of 5.0. At least three consecutive probes should be present to consider a region as containing copy number variation. Matched samples (FFPE and frozen tissue samples) from nine cases were evaluated by both methodologies. The HR-CGH analysis revealed 155 alterations in minimal common regions including 111 losses and 44 genomic gains. Gains at 1q12-q13 and losses at 3p24, 3p25 and 13q31 were significantly associated with lymph node metastasis. Gains at 1q22-q23 and 6q21 and losses at 19q13.1-13.2 were frequently detected in more differentiated (G1/G2) tumor samples. Losses at 3p25 and 15q25-26 showed significant association with earlier TNM stages. Loss at 12q24.3 was associated with cases without lymphatic invasion. The aCGH analysis revealed 38 significant genomic alterations including 21 gains and 17 losses. Gains were detected at 3q, 8q and 11q; losses were found at 3q, 5q, 8q, 9p, 14q, 19p and 21q. The genomic alterations included about 730 genes related to various cellular processes as cell cycle control, cell growth and adhesion, gene transcription and others. Genomic gains at 11q13.2-q13.3 were the most frequent alterations between the cases and gains at 11q13.2 showed significant association (p=0,022) with lymphatic invasion. Genes involved in cell cycle control (CCND1), growth factor (FGF3, -4, -19), Wnt signaling pathway (LRP5) and cell motility (CTTN) are mapped to these regions. Gains at 11q13.2, 11q13.2-q13.3, 11q13.3, and losses at 5q35.2, 9p23-p21.3, 9p21.3, 9p21.3-p21.1, 9p13.3-p13.1, 14q32.12 and 19q13.11 were identified by both aCGH and HR-CGH techniques, suggesting a relevance to these alterations in ESCC development. In this study, it was detected recurrent chromosomal alterations including genes involved in regulation of transcription, signal transduction, cell cycle, cell proliferation and differentiation that could have an impact on tumor development or progression in ESCC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3050. doi:10.1158/1538-7445.AM2011-3050