Copy number changes of target genes in chromosome 3q25.3-qter of esophageal squamous cell carcinoma: TP63is amplified in early carcinogenesis but down-regulated as disease progressed

作     者：Chueh-ChuanYen Yann-JangChen Chin-ChenPan Kai-HsiLu PaulChih-HsuehChen Jiun-YiHsia Jung-TaChen Yu-ChungWu Wen-HuHsu Liang-ShunWang Min-HsiungHuang Biing-ShiungHuang Cheng-PoHu Po-MinChen Chi-HungLin 

作者机构：DivisionofMedicalOncologyDepartmentofMedicineTaipeiVeteransGeneralHospitalandNationalYang-MingUniversitySchoolofMedicineTaipeiTaiwanChina FacultyofLifeScienceNationalYang-MingUniversityTaipeiTaiwanChina DepartmentofPathologyNationalYang-MingUniversityandTaipeiVeteransGeneralHospitalTaiwanChina InstituteofMicrobiologyandImmunologyNationalYang-MingUniversityTaipeiTaiwanChina DivisionofThoracicSurgeryDepartmentofSurgeryTaichungVeteransGeneralHospitalTaichungTaiwanChina DepartmentofPathology.TaichungVeteransGeneralHospitalandDepartmentofPathologyChung-ShanMedicalUniversityTaichungTaiwanChina DivisionofThoracicSurgeryDepartmentofSurgeryTaipeiVeteransGeneralHospitalandNationalYang-MingUniversityTaipeiTaiwanChina InstituteofMicrobiologyandImmunologyNationalYang-MingUniversityandDepartmentofMedicalResearchandEducationTaipeiVeteransGeneralHospitalTaipeiTaiwanChina InstituteofMicrobiologyandImmunologyandInstituteofBiophotonicsNationalYang-MingUniversityTaipeiTaiwanChina 

出 版 物：《World Journal of Gastroenterology》 (世界胃肠病学杂志（英文版）)

年 卷 期：2005年第11卷第9期

页      面：1267-1272页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：Supported by the National Microarray and Gene Expression Analysis Core Facility of the National Research Program for Genomic Medicine at National Yang-Ming University (http://www.ym.edu. tw/microarray) annual project Grant From National Science Council (Grant NO. NSC 92-2314-B-075-055)  Taiwan  China 

主　　题：Chromosomal aberration Comparative genomic hybridization Esophageal neoplasm Immunohistochemistry Quantitative real-time PCR Tissue array Tumor protein 63 

摘      要：AIM: By using comparative genomic hybridization, gain of 3q was found in 45-86% cases of esophageal squamous cell carcinoma (EC-SCC). Chromosome 3q25.3-qter is the minimal common region with several oncogenes found within this region. However, amplification patterns of these genes in EC-SCC have never been reported. The possible association of copy number changes of these genes with pathologic characteristics is still not clear. METHODS: Real-time quantitative PCR (Q-PCR) was performed to analyze the copy number changes of 13 candidate genes within this region in 60 primary tumors of EC-SCC, and possible association of copy number changes with pathologic characteristics was analyzed by statistics. Immunohistochemistry (IHC) study was also performed on another set of 111 primary tumors of EC-SCC to verify the association between TP63 expression change and lymph node metastasis status. RESULTS: The average copy numbers (±SE) per haploid genome of individual genes in 60 samples were (from centromere to telomere): SSR3: 4.19 (±0.69); CCNL1: 5.24 (±0.67); SMC4L1: 2.01 (±0.16); EVI1: 2.02 (±0.12); hTERC. 5.28 (±0.54); SKIL 2.71 (±0.14); EIF5A2. 1.95 (±0.12); ECT2: 9.18 (±1.68); PIK3CA: 8.13 (±1.17); EIF4G1: 1.07 (±0.05); 557: 3.07 (±0.25); TP63: 2.51 (±0.22); TFRC. 2.42 (±0.19). Four clusters of amplification were found: SSR3 and CCLN1 at 3q25.31; hTERC and SKIL at 3q26.2; ECT2 and PIK3CA at 3q26.31-q26.32; and 55T, TP63 and TFRC at 3q27.3-q29. Patients with lymph node metastasis had significantly lower copy number of TP63 in the primary tumor than those without lymph node metastasis. IHC study on tissue arrays also showed that patients with lymph node metastasis have significantly lower TP63 staining score in the primary tumor than those without lymph node metastasis. CONCLUSION: This study showed that different amplification patterns were seen among different genes within 3q25.3-qter in EC-SCC, and several novel candidate oncogenes (SSR3, SMC4L1, ECT2, and SST) were ide