Loss of heterozygosity suggests multiple Genetic alterations in pheochromocytomas and medullary thyroid carcinomas

Sundeep Khosla, V. M. Patel, Ian D Hay, Daniel J Schaid, C. S. Grant, J. A. Van Heerden, Stephen N Thibodeau

Research output: Contribution to journalArticle

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Abstract

Loss of heterozygosity (LOH) at specific loci may help localize tumor suppressor genes involved in the formation of various familial and sporadic tumors. In addition, the genetic loci for a number of familial tumor syndromes have been mapped by linkage analysis. To explore the possible role of tumor suppressor genes in endocrine tumors, we tested 41 pheochromocytomas (34 sporadic and 7 familial) and 11 medullary thyroid cancers (MTC) (10 sporadic and 1 familial) for LOH near a variety of potentially important genetic loci: (a) the multiple endocrine neoplasia type 2A (MEN 2A) locus on chromosome 10; (b) the von Hippel-Lindau locus on 3p; and (c) the p53 and neurofibromatosis 1 loci on 17. We also examined chromosomes Ip and 22q because previous studies in a small number of pheochromocytomas and MTCs suggested LOH in these regions. Background rates for LOH were assessed using several "random" probes. Finally, we examined a number of clinical and histologic characteristics of these tumors for possible correlations with specific genetic alterations. LOH in the region of the MEN 2A locus was uncommon (0% for MTCs, 5% for pheochromocytomas). However, we found significant allelic losses in pheochromocytomas on chromosomes 1p (42%), 3p (16%), 17p (24%), and 22q (31%). We also noted a correlation between LOH on 1p and urinary excretion of metanephrine by these patients (P = 0.02). LOH on 1p, 3p, and 17p also appeared to be associated with increased tumor volume. Analysis of the smaller number of MTCs demonstrated allelic losses on chromosomes Ip and 22q. Our results suggest that tumor formation and/or progression in pheochromocytomas and MTCs involves multiple genes, analogous with the model proposed for colon carcinoma.

Original languageEnglish (US)
Pages (from-to)1691-1699
Number of pages9
JournalJournal of Clinical Investigation
Volume87
Issue number5
StatePublished - May 1991

Fingerprint

Loss of Heterozygosity
Pheochromocytoma
Multiple Endocrine Neoplasia Type 2a
Genetic Loci
Chromosomes
Neoplasms
Tumor Suppressor Genes
Metanephrine
Medullary Thyroid cancer
Chromosomes, Human, Pair 10
Neurofibromatosis 1
Tumor Burden
Colon
Carcinoma

Keywords

  • Allelic losses
  • Familial tumors
  • Multiple endocrine neoplasia
  • Tumor suppressor genes
  • Tumorigenesis

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Loss of heterozygosity suggests multiple Genetic alterations in pheochromocytomas and medullary thyroid carcinomas. / Khosla, Sundeep; Patel, V. M.; Hay, Ian D; Schaid, Daniel J; Grant, C. S.; Van Heerden, J. A.; Thibodeau, Stephen N.

In: Journal of Clinical Investigation, Vol. 87, No. 5, 05.1991, p. 1691-1699.

Research output: Contribution to journalArticle

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