Intragenic allelic loss and promoter hypermethylation of the RIZ1 tumor suppressor gene in parathyroid tumors and pheochromocytomas

Surgery. 2003 Dec;134(6):932-9; discussion 939-40. doi: 10.1016/s0039-6060(03)00422-7.


Background: Loss of heterozygosity (LOH) at chromosome 1p is a common abnormality in both parathyroid tumors and pheochromocytomas. The recently characterized tumor suppressor gene RIZ1, located at 1p36, has emerged as a putative candidate to be involved in endocrine tumorigenesis.

Material: Presence of allelic loss, promoter hypermethylation, and mutational aberrations of the RIZ1 gene were investigated using PCR-based techniques in 47 parathyroid tumors and 23 pheochromocytomas. Gene expression studies used the RNAse protection assay.

Results: RIZ1 mRNA is expressed in pathologic tissues of the parathyroid and adrenal medulla. Thirteen of 47 (28%) parathyroid tumors, and 9/23 (39%) pheochromocytomas displayed LOH within the RIZ1 gene locus. Promoter hypermethylation of RIZ1 was detected in 36% of the parathyroid tumors and was related to LOH at the RIZ1 locus (P=.01), and absence of somatic mutation of the MEN1 gene (P=.044). In the pheochromocytomas, none of the benign tumors, but 2/4 malignant specimens exhibited RIZ1 promoter hypermethylation.

Conclusion: Alteration of the RIZ1 gene locus via intragenic allelic loss and promoter hypermethylation seem common in parathyroid tumors. Inactivation of the RIZ1 gene may cause parathyroid tumorigenesis via a mechanism in which genetic alteration of the MEN1 gene is redundant.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adrenal Gland Neoplasms / genetics*
  • Adult
  • Aged
  • Aged, 80 and over
  • Cell Transformation, Neoplastic / genetics
  • DNA Methylation*
  • DNA-Binding Proteins / genetics*
  • Female
  • Gene Expression / genetics
  • Genes, Tumor Suppressor / physiology*
  • Histone-Lysine N-Methyltransferase
  • Humans
  • Loss of Heterozygosity / genetics*
  • Male
  • Middle Aged
  • Nuclear Proteins / genetics*
  • Parathyroid Neoplasms / genetics*
  • Pheochromocytoma / genetics*
  • Promoter Regions, Genetic / genetics*
  • Transcription Factors / genetics*


  • DNA-Binding Proteins
  • Nuclear Proteins
  • Transcription Factors
  • Histone-Lysine N-Methyltransferase
  • PRDM2 protein, human