Lack of class I HLA expression in neuroblastoma is associated with high N-myc expression and hypomethylation due to loss of the MEMO-1 locus

Oncogene. 1996 Oct 17;13(8):1737-44.


Class I HLA expression is low in neuroblastoma tumours and cell lines. We have recently mapped a modifier of methylation for HLA-C (MEMO-1) to chromosomal bands 1p35-36.1, a region deleted in many neuroblastomas. Hypomethylation of HLA-C is strongly correlated with allelic loss of the MEMO-1 locus. Here, we show that loss of MEMO-1 is associated with hypomethylation of both the 5' and 3' regions of class I HLA loci. We next investigated the relationship between methylation and expression of class I HLA in 28 cell lines of neuroectodermal tumours. Cell lines with hypermethylated HLA-C and HLA-A loci have relatively high expression, while most cell lines with hypomethylated loci have no or a reduced expression. It was reported earlier that high expression of c- or N-myc can suppress class I HLA expression. Remarkably, also N-myc amplification in neuroblastomas is associated with allelic loss of 1p35-36. Therefore, we have analysed the relationships between allelic loss of the MEMO-1 locus, class I HLA methylation and expression, and N-myc amplification and expression. This study shows a tight inter-relationship between these phenomena. Our data suggest a model in which hypomethylation of class I HLA due to loss of the MEMO-1 locus and high N-myc expression could collaborate in the down-regulation of class I HLA expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Fusion
  • Chromosome Deletion*
  • Genes, MHC Class I*
  • Genes, myc*
  • HLA-A Antigens / genetics
  • HLA-C Antigens / genetics
  • Humans
  • Methylation
  • Neuroblastoma / genetics*
  • Neuroblastoma / pathology
  • RNA, Messenger / genetics
  • Tumor Cells, Cultured


  • HLA-A Antigens
  • HLA-C Antigens
  • RNA, Messenger