Loss of heterozygosity in multistage carcinogenesis of esophageal carcinoma at high-incidence area in Henan Province, China

Abstract

Aim: Microsatellites are the repeated DNA sequences scattered widely within the genomes and closely linked with many important genes. This study was designed to characterize the changes of microsatellite DNA loss of heterozygosity (LOH) in esophageal carcinogenesis.

Methods: Allelic deletions in 32 cases of matched precancerous, cancerous and normal tissues were examined by syringe microdissection under an anatomic microscope and microsatellite polymorphism analysis using 15 polymorphic markers on chromosomes 3p, 5q, 6p, 9p, 13q, 17p, 17q and 18q.

Results: Microsatellite DNA LOH was observed in precancerous and cancerous tissues, except D9S1752. The rate of LOH increased remarkably with the lesions progressed from basal cell hyperplasia (BCH) to squamous cell carcinoma (SCC) (P<0.05). Three markers, D9S171, D13S260 and TP53, showed the highest incidence of LOH (>60%). LOH loci were different in precancerous and cancerous tissues. LOH in D3S1234 and TP53 was the common event in different lesions from the same patients.

Conclusion: Microsatellite DNA LOH occurs in early stage of human esophageal carcinogenesis, even in BCH. With the lesion progressed, gene instability increases, the accumulation of this change may be one of the important mechanisms driving precancerous lesions to cancer.

Figure 1

Allelic deletion patterns in TP53 microsatellite loci. Arrows indicate LOH in different lesions. B: basal cell hyperplasia (BCH), D: dysplasia (DYS), C: carcinoma in situ (CIS), S: squamous cell carcinoma(SCC), N: normal tissue, A: LOH in BCH; B: LOH in DYS; C: LOH in CIS; D: LOH in SCC.

Figure 2

Allelic deletion patterns of various microsatellite markers in ESCC. Paired tumor DNA (T) and non-neoplastic DNA (N) were examined for each case. Arrows indicate LOH in tumor samples. A: D3S966 LOH; B: D6S497 LOH; C: D9S1752 LOH; D: D13S233 LOH; E: TP53 LOH; F: D18S858 LOH.

Figure 3

Distributions of microsatellite DNA-LOH in different precancerous lesions of esophagus FAL: fractional allelic loss for each tumor ○ retention of heterozygosity ■ loss of heterozygosity Ø uninformative, X not done.