Microsatellite alteration at chromosome 11 in primary human nasopharyngeal carcinoma in Taiwan.
Nasopharyngeal carcinoma (NPC) is one of the common cancers in Taiwan but is rare in western countries. The development of NPC involves multiple genetic changes in tumorigenesis and progression of the disease. To better understand genetic alterations in chromosome 11 which occur in human (NPC), we examined tumor specimens and corresponding non-cancerous tissue from 30 cases of NPC, using five microsatellite polymorphic markers whose location has previously been defined. To determine the clinical characteristics of MSI(+) or LOH, we performed correlation analysis of the findings with clinicopathological parameters. Loss of heterozygosity (LOH) was identified in 18 (60%) of 30 cases on at least one of the five markers. A high frequency of LOH was found at the two loci: D11S912 (7/30, 23.33%) and D11S934 (6/30, 20.00%), both of which are located within 11q23-24. We also found that 14 specimens (14/30, 46.67%) exhibited microsatellite instability (MSI(+)). Five (5/30, 16.67%) specimens exhibited MSI(+) in the transformation growth factor beta receptor type II (TGF-beta RII) exon 3 which also exhibited on chromosome 11. LOH was found to be significantly correlated with the T (tumor size) value (P=0.022) of Ho's system. MSI(+) showed a significant correlation with the N (lymph node) value of the UICC system (P=0.031). Our results suggest that multiple putative tumor suppressor genes on chromosome 11 play a role in the development of NPC. MSI(+) expression showed a predisposition to occur in the late stage of NPC while LOH tended to occur in early stages of NPC. The behavior of mutated TGF-beta RII exon 3, which appeared to serve as a dysfunction brake during nasopharyngeal carcinogenesis, may be a target gene in the defected mismatch repair system.
Harn
Horng-Jyh
HJ
Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan. duke@ndmc.ndmctsgh.edu.tw
Fan
Hueng-Chuen
HC
Chen
Cheng-Jueng
CJ
Tsai
Nu-Man
NM
Yen
Chung-Yang
CY
Huang
Su-Chin
SC
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D001345:Autoradiography; D016009:Chi-Square Distribution; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D004591:Electrophoresis, Polyacrylamide Gel / Q000379:methods; D005260:Female; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics*; D008875:Middle Aged; D009303:Nasopharyngeal Neoplasms / Q000235:genetics*; D015345:Oligonucleotide Probes; D016133:Polymerase Chain Reaction / Q000379:methods; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics; D018709:Statistics, Nonparametric; D013624:Taiwan
D015345:Oligonucleotide Probes; D018125:Receptors, Transforming Growth Factor beta