Chromosome 3p12.3-p14.2 and 3q26.2-q26.32 are genomic markers for prognosis of advanced nasopharyngeal carcinoma

Jim Jinn Chyuan Sheu, Chia Huei Lee, Jenq Yuh Ko, George S W Tsao, Chung Chun Wu, Chih Yeu Fang, Fuu Jen Tsai, Chun Hung Hua, Chi Long Chen, Jen Yang Chen

Research output: Contribution to journalArticle

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Abstract

Purpose: Nasopharyngeal carcinoma is an epithelial malignancy with a remarkable racial and geographic distribution. Previous cytogenetic studies have shown nasopharyngeal carcinoma to be characterized by gross genomic aberrations. However, identification of susceptible gene loci in advanced nasopharyngeal carcinoma has been poorly discussed. Experimental Design: A genome-wide survey of gene copy number changes was initiated with two nasopharyngeal carcinoma cell lines by array-based comparative genomic hybridization analysis. These alterations were confirmed by a parallel analysis with the data from the gene expression microarray and were validated by quantitative PCR. Clinical association of the defined target genes was analyzed by fluorescence in situ hybridization on 48 metastatic tumors. Results: A high percentage of genes were consistently altered in dosage and expression levels with gain on 3q26.2-q26.32 and losses on 3p12.3-p14.2 and 9p21.3-p23. Six candidate genes, GPR160 (3q26.2-q27), SKIL (3q26), ADAMTS9 (3p14.2-p14.3), LRIG1 (3p14), MPDZ (9p22-p24), and ADFP (9p22.1) were validated by quantitative PCR. Fluorescence in situ hybridization studies revealed amplification of GPR160 (in 25% of cases) and SKIL (33%); and deletion of ADAMTS9 (30%), LRIG1 (35%), MPDZ (15%), and ADFP (15%). Clinical association analyses indicated a poor survival rate with genetic alterations at the defined 3p deletion (P = 0.0012) and the 3q amplification regions (P = 0.0114). Conclusion: The combined microarray technologies suggested novel candidate oncogenes, amplification of GPR160 and SKIL at 3q26.2-q26.32, and deletion of tumor suppressor genes ADAMTS9 and LRIG1 at 3p12.3-p14.2. Altered expression of these genes may be responsible for malignant progression and could be used as potential markers for nasopharyngeal carcinoma.

Original languageEnglish
Pages (from-to)2709-2716
Number of pages8
JournalCancer Epidemiology Biomarkers and Prevention
Volume18
Issue number10
DOIs
Publication statusPublished - Oct 2009

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Chromosomes
Fluorescence In Situ Hybridization
Genes
Gene Expression
Polymerase Chain Reaction
Comparative Genomic Hybridization
Gene Dosage
Tumor Suppressor Genes
Oncogenes
Cytogenetics
Neoplasms
Research Design
Nasopharyngeal carcinoma
Genome
Technology
Cell Line

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

Cite this

Chromosome 3p12.3-p14.2 and 3q26.2-q26.32 are genomic markers for prognosis of advanced nasopharyngeal carcinoma. / Sheu, Jim Jinn Chyuan; Lee, Chia Huei; Ko, Jenq Yuh; Tsao, George S W; Wu, Chung Chun; Fang, Chih Yeu; Tsai, Fuu Jen; Hua, Chun Hung; Chen, Chi Long; Chen, Jen Yang.

In: Cancer Epidemiology Biomarkers and Prevention, Vol. 18, No. 10, 10.2009, p. 2709-2716.

Research output: Contribution to journalArticle

Sheu, Jim Jinn Chyuan ; Lee, Chia Huei ; Ko, Jenq Yuh ; Tsao, George S W ; Wu, Chung Chun ; Fang, Chih Yeu ; Tsai, Fuu Jen ; Hua, Chun Hung ; Chen, Chi Long ; Chen, Jen Yang. / Chromosome 3p12.3-p14.2 and 3q26.2-q26.32 are genomic markers for prognosis of advanced nasopharyngeal carcinoma. In: Cancer Epidemiology Biomarkers and Prevention. 2009 ; Vol. 18, No. 10. pp. 2709-2716.
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abstract = "Purpose: Nasopharyngeal carcinoma is an epithelial malignancy with a remarkable racial and geographic distribution. Previous cytogenetic studies have shown nasopharyngeal carcinoma to be characterized by gross genomic aberrations. However, identification of susceptible gene loci in advanced nasopharyngeal carcinoma has been poorly discussed. Experimental Design: A genome-wide survey of gene copy number changes was initiated with two nasopharyngeal carcinoma cell lines by array-based comparative genomic hybridization analysis. These alterations were confirmed by a parallel analysis with the data from the gene expression microarray and were validated by quantitative PCR. Clinical association of the defined target genes was analyzed by fluorescence in situ hybridization on 48 metastatic tumors. Results: A high percentage of genes were consistently altered in dosage and expression levels with gain on 3q26.2-q26.32 and losses on 3p12.3-p14.2 and 9p21.3-p23. Six candidate genes, GPR160 (3q26.2-q27), SKIL (3q26), ADAMTS9 (3p14.2-p14.3), LRIG1 (3p14), MPDZ (9p22-p24), and ADFP (9p22.1) were validated by quantitative PCR. Fluorescence in situ hybridization studies revealed amplification of GPR160 (in 25{\%} of cases) and SKIL (33{\%}); and deletion of ADAMTS9 (30{\%}), LRIG1 (35{\%}), MPDZ (15{\%}), and ADFP (15{\%}). Clinical association analyses indicated a poor survival rate with genetic alterations at the defined 3p deletion (P = 0.0012) and the 3q amplification regions (P = 0.0114). Conclusion: The combined microarray technologies suggested novel candidate oncogenes, amplification of GPR160 and SKIL at 3q26.2-q26.32, and deletion of tumor suppressor genes ADAMTS9 and LRIG1 at 3p12.3-p14.2. Altered expression of these genes may be responsible for malignant progression and could be used as potential markers for nasopharyngeal carcinoma.",
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T1 - Chromosome 3p12.3-p14.2 and 3q26.2-q26.32 are genomic markers for prognosis of advanced nasopharyngeal carcinoma

AU - Sheu, Jim Jinn Chyuan

AU - Lee, Chia Huei

AU - Ko, Jenq Yuh

AU - Tsao, George S W

AU - Wu, Chung Chun

AU - Fang, Chih Yeu

AU - Tsai, Fuu Jen

AU - Hua, Chun Hung

AU - Chen, Chi Long

AU - Chen, Jen Yang

PY - 2009/10

Y1 - 2009/10

N2 - Purpose: Nasopharyngeal carcinoma is an epithelial malignancy with a remarkable racial and geographic distribution. Previous cytogenetic studies have shown nasopharyngeal carcinoma to be characterized by gross genomic aberrations. However, identification of susceptible gene loci in advanced nasopharyngeal carcinoma has been poorly discussed. Experimental Design: A genome-wide survey of gene copy number changes was initiated with two nasopharyngeal carcinoma cell lines by array-based comparative genomic hybridization analysis. These alterations were confirmed by a parallel analysis with the data from the gene expression microarray and were validated by quantitative PCR. Clinical association of the defined target genes was analyzed by fluorescence in situ hybridization on 48 metastatic tumors. Results: A high percentage of genes were consistently altered in dosage and expression levels with gain on 3q26.2-q26.32 and losses on 3p12.3-p14.2 and 9p21.3-p23. Six candidate genes, GPR160 (3q26.2-q27), SKIL (3q26), ADAMTS9 (3p14.2-p14.3), LRIG1 (3p14), MPDZ (9p22-p24), and ADFP (9p22.1) were validated by quantitative PCR. Fluorescence in situ hybridization studies revealed amplification of GPR160 (in 25% of cases) and SKIL (33%); and deletion of ADAMTS9 (30%), LRIG1 (35%), MPDZ (15%), and ADFP (15%). Clinical association analyses indicated a poor survival rate with genetic alterations at the defined 3p deletion (P = 0.0012) and the 3q amplification regions (P = 0.0114). Conclusion: The combined microarray technologies suggested novel candidate oncogenes, amplification of GPR160 and SKIL at 3q26.2-q26.32, and deletion of tumor suppressor genes ADAMTS9 and LRIG1 at 3p12.3-p14.2. Altered expression of these genes may be responsible for malignant progression and could be used as potential markers for nasopharyngeal carcinoma.

AB - Purpose: Nasopharyngeal carcinoma is an epithelial malignancy with a remarkable racial and geographic distribution. Previous cytogenetic studies have shown nasopharyngeal carcinoma to be characterized by gross genomic aberrations. However, identification of susceptible gene loci in advanced nasopharyngeal carcinoma has been poorly discussed. Experimental Design: A genome-wide survey of gene copy number changes was initiated with two nasopharyngeal carcinoma cell lines by array-based comparative genomic hybridization analysis. These alterations were confirmed by a parallel analysis with the data from the gene expression microarray and were validated by quantitative PCR. Clinical association of the defined target genes was analyzed by fluorescence in situ hybridization on 48 metastatic tumors. Results: A high percentage of genes were consistently altered in dosage and expression levels with gain on 3q26.2-q26.32 and losses on 3p12.3-p14.2 and 9p21.3-p23. Six candidate genes, GPR160 (3q26.2-q27), SKIL (3q26), ADAMTS9 (3p14.2-p14.3), LRIG1 (3p14), MPDZ (9p22-p24), and ADFP (9p22.1) were validated by quantitative PCR. Fluorescence in situ hybridization studies revealed amplification of GPR160 (in 25% of cases) and SKIL (33%); and deletion of ADAMTS9 (30%), LRIG1 (35%), MPDZ (15%), and ADFP (15%). Clinical association analyses indicated a poor survival rate with genetic alterations at the defined 3p deletion (P = 0.0012) and the 3q amplification regions (P = 0.0114). Conclusion: The combined microarray technologies suggested novel candidate oncogenes, amplification of GPR160 and SKIL at 3q26.2-q26.32, and deletion of tumor suppressor genes ADAMTS9 and LRIG1 at 3p12.3-p14.2. Altered expression of these genes may be responsible for malignant progression and could be used as potential markers for nasopharyngeal carcinoma.

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