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


METHODS
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).


CONCLUSIONS
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.
Sheu
Jim Jinn-Chyuan
JJ
Department of Medical Research, China Medical University Hospital, Taichung, Taiwan.
Lee
Chia-Huei
CH
Ko
Jenq-Yuh
JY
Tsao
George S W
GS
Wu
Chung-Chun
CC
Fang
Chih-Yeu
CY
Tsai
Fuu-Jen
FJ
Hua
Chun-Hung
CH
Chen
Chi-Long
CL
Chen
Jen-Yang
JY
D045744:Cell Line, Tumor; D002893:Chromosomes, Human, Pair 3; D005784:Gene Amplification; D018628:Gene Dosage; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D015894:Genome, Human; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D009303:Nasopharyngeal Neoplasms / Q000235:genetics* / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis