Endocrine

, Volume 44, Issue 2, pp 489–495

Allelic imbalance in sporadic parathyroid carcinoma and evidence for its de novo origins

  • Jessica Costa-Guda
  • Yasuo Imanishi
  • Nallasivam Palanisamy
  • Norihiko Kawamata
  • H. Phillip Koeffler
  • R. S. K. Chaganti
  • Andrew Arnold
Original Article

DOI: 10.1007/s12020-013-9903-4

Cite this article as:
Costa-Guda, J., Imanishi, Y., Palanisamy, N. et al. Endocrine (2013) 44: 489. doi:10.1007/s12020-013-9903-4

Abstract

Parathyroid cancer is a rare, clinically aggressive cause of primary hyperparathyroidism, and whether these malignancies generally evolve from pre-existing benign adenomas or arise de novo is unclear. Furthermore, while inactivation of the CDC73 (HRPT2) tumor suppressor gene, encoding parafibromin, is a major contributor, other genes essential to parathyroid carcinogenesis remain unknown. We sought to identify genomic regions potentially harboring such oncogenes or tumor suppressor genes, and to gain insight into the origins and molecular relationship of malignant versus benign parathyroid tumors. We performed genome-wide copy-number and loss of heterozygosity analysis using Affymetrix 50K SNP mapping arrays and/or comparative genomic hybridization on 16 primary parathyroid carcinomas, local recurrences or distant metastases, and matched normal controls, from 10 individuals. Recurrent regions of allelic loss were observed on chromosomes 1p, 3, and 13q suggesting that key parathyroid tumor suppressor genes are located in these chromosomal locations. Recurrent allelic gains were seen on chromosomes 1q and 16, suggesting the presence of parathyroid oncogenes on these chromosomes. Importantly, the most common alteration in benign parathyroid adenomas, loss of 11q, was not found as a recurrent change in the malignant parathyroid tissues. Molecular allelotyping using highly polymorphic microsatellite markers provided further confirmation that the prevalence of 11q loss is markedly and significantly lower in carcinomas as compared with adenomas. Our observations provide molecular support for the concept that sporadic parathyroid cancer usually arises de novo, rather than evolving from a pre-existing typical benign adenoma. Furthermore, these results help direct future investigation to ultimately determine which of the candidate genes in these chromosomal locations make significant contributions to the molecular pathogenesis of parathyroid cancer.

Keywords

Primary hyperparathyroidism Parathyroid carcinoma Allelic imbalance DNA microarray 

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Jessica Costa-Guda
    • 1
  • Yasuo Imanishi
    • 1
    • 2
  • Nallasivam Palanisamy
    • 3
  • Norihiko Kawamata
    • 4
  • H. Phillip Koeffler
    • 4
  • R. S. K. Chaganti
    • 3
  • Andrew Arnold
    • 1
    • 5
  1. 1.University of Connecticut Health CenterFarmingtonUSA
  2. 2.Osaka City University Graduate School of MedicineOsakaJapan
  3. 3.Memorial Sloan-Kettering Cancer CenterNew YorkUSA
  4. 4.Cedars-Sinai Medical CenterLos AngelesUSA
  5. 5.Center for Molecular MedicineUniversity of Connecticut School of MedicineFarmingtonUSA

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