Loss of heterozygosity at the human leukocyte antigen locus in thymic epithelial tumors

Abstract

Background: To study the relationship between loss of heterozygosity (LOH) at the human leukocyte antigen (HLA) locus and the pathogenicity and clinicopathological features of thymic epithelial tumors (TET).

Methods: Tumor and adjacent normal tissues were isolated from 36 TET patients. Five microsatellite loci (D6S1666, D6S265, D6S273, DS6276, and D6S291) within the HLA locus were amplified by polymerase chain reaction. DNA sequencing was used to measure the frequency of microsatellite LOH.

Results: LOH was identified in at least one locus in 83.6% of TET patients. LOH frequency at D6S1666, D6S265, D6S273, D6S276, and D6S291 was 44.4%, 16.7%, 30.5%, 38.9%, and 36.1% respectively. There was no significant association between LOH frequency in TET with tumor severity, or in the presence or absence of myasthenia gravis.

Conclusions: D6S1666, D6S265, D6S273, DS6S276, and D6S29 are sensitive loci for studying microsatellite LOH in TET. LOH within the HLA complex is implicated in the occurrence and development of TET, with the HLA-DQA1 gene likely involved. However, an understanding of the relationship between LOH and the clinicopathological features of TET requires a larger sample size than that of the present study.

Keywords: Human leukocyte antigen (HLA); loss of heterozygosity (LOH); microsatellite; thymic epithelial tumor (TET).

Figure 1

Graphic representation of human leukocyte antigen (HLA) microsatellite loci on the short arm of chromosome 6.

Figure 2

Agarose gel electrophoresis of polymerase chain reaction products following amplification of five microsatellite regions within the human leukocyte antigen gene. M: marker, T: tumor tissue, N: normal tissue, B: blank. M₁ from top to bottom: 600, 500, 400, 300, 200, and 100 bp; M₂ from top to bottom: 500, 400, 350, 300, 250, 200, 150, 100, and 50 bp.