Gain of chromosome 6 status does not influence HLA-expression in uveal melanoma

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Abstract

Purpose

Chromosomal aberrations and the inflammatory phenotype have been identified as predictive factors for survival of uveal melanoma (UM). The mechanism by which these factors are linked remains obscure. We took the human leukocyte antigen (HLA), located on chromosome 6p as marker for inflammation and studied whether aberrations of chromosome 6p influenced the HLA expression in UM.

Methods

SNP-array copy number analysis and gene expression profiling were performed on 28 uveal melanomas of patients who underwent enucleation between 1999 and 2004 at the Leiden University Medical Center, Leiden, in The Netherlands. UM protein expression of HLA-A, -B and –DR was measured with immunohistochemistry. The status of chromosome 3, 6p, and gene expression of HLA and HLA regulators were analyzed, as well as protein expression of HLA.

Results

Gain of 6p was present in 8 cases (29%) and not related with survival. An increased gene expression was seen in the group who died due to metastatic UM for HLA-A and –B, and B2M. Gene expression correlated with protein expression for HLA-A, HLA-B, but not with HLA-DR. Tumors did not differ in level of HLA protein expression, HLA gene expression, and HLA regulator gene expression with regard to chromosome 6p status.

Conclusion

High HLA gene- and protein expression in UM are not influenced by gain of 6p. Yet for the first time we demonstrated that in UM an increased expression of HLA class I genes correlated with the elevated protein expression of HLA class I.

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