Prognostic Impact of Array-based Genomic Profiles in Esophageal Squamous Cell Cancer

A 32 k aCGH platform was used for high resolution mapping of copy number changes in 30 stage I-IV ESCC. Potential interdependent alterations and deranged pathways were identified and copy number changes were correlated to stage, differentiation and survival.Copy number alterations affected median 19% of the genome and included recurrent gains of chromosome regions 5p, 7p, 7q, 8q, 10q, 11q, 12p, 14q, 16p, 17p, 19p, 19q, and 20q and losses of 3p, 5q, 8p, 9p and 11q. High-level amplifications were observed in 30 regions and recurrently involved 7p11 (EGFR), 11q13 (MYEOV, CCND1, FGF4, FGF3, PPFIA, FAD, TMEM16A, CTTS and SHANK2) and 11q22 (PDFG). Gain of 7p22.3 predicted nodal metastases and gains of 1p36.32 and 19p13.3 independently predicted poor survival in multivariate analysis.aCGH profiling verified genetic complexity in ESCC and herein identified imbalances of multiple central tumorigenic pathways. Distinct gains correlate with clinicopathological variables and independently predict survival, suggesting clinical applicability of genomic profiling in ESCC.Esophageal squamous cell carcinoma (ESCC) is a major cause of cancer-related mortality worldwide. Despite advances in diagnostic methods and combined treatment modalities, the majority of the tumors are diagnosed at advanced stages and the overall 5-year survival rate remains 40%. ESCC develops through a multistep process from dysplasia, through carcinoma in situ to invasive carcinoma, and the acquisition of genetic alterations is tightly related to the dysplasia-carcinoma sequence [1]. The characterization of genetic alterations inherently linked to ESCC development and an in-depth understanding of the molecular mechanisms underlying carcinogenesis and growth control may therefore provide information relevant for early tumor detection, refined prognosis and development of novel targeted therapeutics.Loss of heterozygozity (LOH) studies and conventional comparative genomic hybridization (CGH) analyses have demonst