Characterization of genetic alteration patterns in human esophageal squamous cell carcinoma using selected microsatellite markers spanning multiple loci.
In order to identify representative genetic alterations in esophageal squamous cell carcinomas (ESCC) and useful markers for future early detection, 34 ESCC samples with neighboring normal epithelia and 30 esophageal biopsy samples from Linzhou, P.R. China, were studied. Of the 38 microsatellite markers selected, half were linked with tumor suppressors. More than 40% of the tumor samples showed loss of heterozygosity (LOH) in at least one of the eight markers, D3S1067 and D3S1561 (both linked to hMLH1 locus), FABP2, D4S1613, D9S171 (p14ARF, p15INK4b, p16INK4a loci), Rb1 (intron), p53-2 (intron), and NM23-H1. Most of the 38 microsatellite markers did not display microsatellite instability (MSI) in more than 30% of the tumor samples, except D9S942 (p14ARF, p15INK4b, p16INK4a loci) and Bat26, which showed frequency at 32 and 41%, respectively. Of all the ESCC samples examined, 20 samples exhibited LOH in 25% or more of the informative markers. Three samples displayed MSI in more than 30% of the markers, indicating that MSI might be an important event in these subset ESCC cases. Statistically significant correlations were found between LOH of the hMLH1 locus and the general LOH status of the sample, and between the LOH of the hMLH1 locus and p53 mutations. In addition, correlation was found between MSI in D3S1067/D3S1561 and the general MSI status in the samples. However, MSI in the introns of hMLH1 and hMSH2 were not correlated with the general MSI status of the tumors. LOH analysis was also performed in 30 esophageal biopsy samples containing precancerous lesions with matching blood samples using nine microsatellite markers selected from the above studies. LOH frequence ranged from 0 to 33% in informative cases, mostly in the 9p21 and p53 gene regions, suggesting these regions are possible targets of genomic instability in early stage ESCC carcinogenesis. The results demonstrate the degree of genetic alterations at different loci of the chromosomes. Some of the microsatellite markers may be useful for the early detection of ESCC.
Cai
Yuyang Christine
YC
Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854-8020, USA.
So
Chi K
CK
Nie
Alex Yan
AY
Song
Yunlong
Y
Yang
Guang-Yu
GY
Wang
Li-Dong
LD
Zhao
Xin
X
Kinzy
Terri Goss
TG
Yang
Chung S
CS
D000483:Alleles; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D018450:Disease Progression; D004938:Esophageal Neoplasms / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D005787:Gene Frequency; D042822:Genomic Instability; D006801:Humans; D019656:Loss of Heterozygosity; D018895:Microsatellite Repeats / Q000235:genetics*; D008957:Models, Genetic