title: Genome-wide screening for genetic alterations in esophageal cancer by aCGH identifies 11q13 amplification oncogenes associated with nodal metastasis.
abstract: BACKGROUND
  Esophageal squamous cell carcinoma (ESCC) is highly prevalent in China and other Asian countries, as a major cause of cancer-related mortality. ESCC displays complex chromosomal abnormalities, including multiple structural and numerical aberrations. Chromosomal abnormalities, such as recurrent amplifications and homozygous deletions, directly contribute to tumorigenesis through altering the expression of key oncogenes and tumor suppressor genes.
  
  
  RESULTS
  To understand the role of genetic alterations in ESCC pathogenesis and identify critical amplification/deletion targets, we performed genome-wide 1-Mb array comparative genomic hybridization (aCGH) analysis for 10 commonly used ESCC cell lines. Recurrent chromosomal gains were frequently detected on 3q26-27, 5p15-14, 8p12, 8p22-24, 11q13, 13q21-31, 18p11 and 20q11-13, with frequent losses also found on 8p23-22, 11q22, 14q32 and 18q11-23. Gain of 11q13.3-13.4 was the most frequent alteration in ESCC. Within this region, CCND1 oncogene was identified with high level of amplification and overexpression in ESCC, while FGF19 and SHANK2 was also remarkably over-expressed. Moreover, a high concordance (91.5%) of gene amplification and protein overexpression of CCND1 was observed in primary ESCC tumors. CCND1 amplification/overexpression was also significantly correlated with the lymph node metastasis of ESCC.
  
  
  CONCLUSIONS
  These findings suggest that genomic gain of 11q13 is the major mechanism contributing to the amplification. Novel oncogenes identified within the 11q13 amplicon including FGF19 and SHANK2 may play important roles in ESCC tumorigenesis.
authors: Department of Pathology, Cancer Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing, China.
authors: Jianming
authors: J
authors: Ying
authors: Ling
authors: L
authors: Shan
authors: Jisheng
authors: J
authors: Li
authors: Lan
authors: L
authors: Zhong
authors: Liyan
authors: L
authors: Xue
authors: Hong
authors: H
authors: Zhao
authors: Lili
authors: L
authors: Li
authors: Cordelia
authors: C
authors: Langford
authors: Lei
authors: L
authors: Guo
authors: Tian
authors: T
authors: Qiu
authors: Ning
authors: N
authors: Lu
authors: Qian
authors: Q
authors: Tao
mesh_terms: D045744:Cell Line, Tumor; D002880:Chromosomes, Human, Pair 11; D055028:Comparative Genomic Hybridization; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology; D055106:Genome-Wide Association Study; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008207:Lymphatic Metastasis / Q000235:genetics*; D009857:Oncogenes; D016133:Polymerase Chain Reaction; D015398:Signal Transduction; D046888:Tissue Array Analysis; D051176:beta Catenin / Q000378:metabolism
chemical_list: D051176:beta Catenin