Copy number changes of target genes in chromosome 3q25.3-qter of esophageal squamous cell carcinoma

TP63 is amplified in early carcinogenesis but down-regulated as disease progressed

Chueh Chuan Yen, Yann Jang Chen, Chin Chen Pan, Kai Hsi Lu, Paul Chih Hsueh Chen, Jiun Yi Hsia, Jung Ta Chen, Yu Chung Wu, Wen Hu Hsu, Liang Shun Wang, Min Hsiung Huang, Biing Shiung Huang, Cheng Po Hu, Po Min Chen, Chi Hung Lin

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

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); SST: 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 SST, 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 identified. TP63 is amplified in early stage of EC-SCC carcinogenesis but down-regulated in advanced stage of disease.

Original languageEnglish
Pages (from-to)1267-1272
Number of pages6
JournalWorld Journal of Gastroenterology
Volume11
Issue number9
Publication statusPublished - Mar 7 2005
Externally publishedYes

Fingerprint

Carcinogenesis
Chromosomes
Lymph Nodes
Neoplasm Metastasis
Genes
Oncogenes
Neoplasms
Immunohistochemistry
Comparative Genomic Hybridization
Gene Dosage
Centromere
Gene Amplification
Haploidy
Telomere
Real-Time Polymerase Chain Reaction
Esophageal Squamous Cell Carcinoma
Genome
Staining and Labeling

Keywords

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

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Copy number changes of target genes in chromosome 3q25.3-qter of esophageal squamous cell carcinoma : TP63 is amplified in early carcinogenesis but down-regulated as disease progressed. / Yen, Chueh Chuan; Chen, Yann Jang; Pan, Chin Chen; Lu, Kai Hsi; Chen, Paul Chih Hsueh; Hsia, Jiun Yi; Chen, Jung Ta; Wu, Yu Chung; Hsu, Wen Hu; Wang, Liang Shun; Huang, Min Hsiung; Huang, Biing Shiung; Hu, Cheng Po; Chen, Po Min; Lin, Chi Hung.

In: World Journal of Gastroenterology, Vol. 11, No. 9, 07.03.2005, p. 1267-1272.

Research output: Contribution to journalArticle

Yen, CC, Chen, YJ, Pan, CC, Lu, KH, Chen, PCH, Hsia, JY, Chen, JT, Wu, YC, Hsu, WH, Wang, LS, Huang, MH, Huang, BS, Hu, CP, Chen, PM & Lin, CH 2005, 'Copy number changes of target genes in chromosome 3q25.3-qter of esophageal squamous cell carcinoma: TP63 is amplified in early carcinogenesis but down-regulated as disease progressed', World Journal of Gastroenterology, vol. 11, no. 9, pp. 1267-1272.
Yen, Chueh Chuan ; Chen, Yann Jang ; Pan, Chin Chen ; Lu, Kai Hsi ; Chen, Paul Chih Hsueh ; Hsia, Jiun Yi ; Chen, Jung Ta ; Wu, Yu Chung ; Hsu, Wen Hu ; Wang, Liang Shun ; Huang, Min Hsiung ; Huang, Biing Shiung ; Hu, Cheng Po ; Chen, Po Min ; Lin, Chi Hung. / Copy number changes of target genes in chromosome 3q25.3-qter of esophageal squamous cell carcinoma : TP63 is amplified in early carcinogenesis but down-regulated as disease progressed. In: World Journal of Gastroenterology. 2005 ; Vol. 11, No. 9. pp. 1267-1272.
@article{9d18d6b9ace747a386c609486fe51038,
title = "Copy number changes of target genes in chromosome 3q25.3-qter of esophageal squamous cell carcinoma: TP63 is amplified in early carcinogenesis but down-regulated as disease progressed",
abstract = "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); SST: 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 SST, 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 identified. TP63 is amplified in early stage of EC-SCC carcinogenesis but down-regulated in advanced stage of disease.",
keywords = "Chromosomal aberration, Comparative genomic hybridization, Esophageal neoplasm, Immunohistochemistry, Quantitative real-time PCR, Tissue array, Tumor protein 63",
author = "Yen, {Chueh Chuan} and Chen, {Yann Jang} and Pan, {Chin Chen} and Lu, {Kai Hsi} and Chen, {Paul Chih Hsueh} and Hsia, {Jiun Yi} and Chen, {Jung Ta} and Wu, {Yu Chung} and Hsu, {Wen Hu} and Wang, {Liang Shun} and Huang, {Min Hsiung} and Huang, {Biing Shiung} and Hu, {Cheng Po} and Chen, {Po Min} and Lin, {Chi Hung}",
year = "2005",
month = "3",
day = "7",
language = "English",
volume = "11",
pages = "1267--1272",
journal = "World Journal of Gastroenterology",
issn = "1007-9327",
publisher = "WJG Press",
number = "9",

}

TY - JOUR

T1 - Copy number changes of target genes in chromosome 3q25.3-qter of esophageal squamous cell carcinoma

T2 - TP63 is amplified in early carcinogenesis but down-regulated as disease progressed

AU - Yen, Chueh Chuan

AU - Chen, Yann Jang

AU - Pan, Chin Chen

AU - Lu, Kai Hsi

AU - Chen, Paul Chih Hsueh

AU - Hsia, Jiun Yi

AU - Chen, Jung Ta

AU - Wu, Yu Chung

AU - Hsu, Wen Hu

AU - Wang, Liang Shun

AU - Huang, Min Hsiung

AU - Huang, Biing Shiung

AU - Hu, Cheng Po

AU - Chen, Po Min

AU - Lin, Chi Hung

PY - 2005/3/7

Y1 - 2005/3/7

N2 - 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); SST: 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 SST, 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 identified. TP63 is amplified in early stage of EC-SCC carcinogenesis but down-regulated in advanced stage of disease.

AB - 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); SST: 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 SST, 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 identified. TP63 is amplified in early stage of EC-SCC carcinogenesis but down-regulated in advanced stage of disease.

KW - Chromosomal aberration

KW - Comparative genomic hybridization

KW - Esophageal neoplasm

KW - Immunohistochemistry

KW - Quantitative real-time PCR

KW - Tissue array

KW - Tumor protein 63

UR - http://www.scopus.com/inward/record.url?scp=20144381465&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=20144381465&partnerID=8YFLogxK

M3 - Article

VL - 11

SP - 1267

EP - 1272

JO - World Journal of Gastroenterology

JF - World Journal of Gastroenterology

SN - 1007-9327

IS - 9

ER -