Loss of heterozygosity at the SS receptor type 5 locus in human GH- and TSH-secreting pituitary adenomas

M. Filopanti, E. Ballarè, A. G. Lania, S. Bondioni, U. Verga, M. Locatelli, L. M. Zavanone, M. Losa, S. Gelmini, A. Peri, C. Orlando, P. Beck-Peccoz, Anna Spada

Research output: Contribution to journalArticle

Abstract

SS receptor types 2 and 5 (sst2 and sst5) are involved in the control of secretion and proliferation of normal and tumoral somatotrophs and thyrotrophs. The mechanisms leading to reduced responsiveness to SS analogues in patients with pituitary tumors are poorly understood. The aim of the study was to verify the possible loss of heterozygosity (LOH) at the sst5 gene locus in somatotroph and thyrotroph adenomas by screening leukocyte and tumor DNA for two single nucleotide polymorphisms, i.e. C1004T leading to P335L change and T-461C in the 5′-upstream region. Among the 13 informative samples, 1 GH- and 1 TSH-secreting adenoma showed LOH at sst5 gene locus with the retention of Leu335 variant. By analyzing other polymorphic markers spanning from telomere to 16p13.3-13.2 boundaries, DNA deletion of at least 1 megabase was found in both tumors. LOH in thyrotroph adenoma was associated with unusual tumor aggressiveness that required a second surgery and resistance to SS analogs, while no obvious phenotype was identified in the case of the somatotroph adenoma. In conclusions, LOH at the sst5 gene locus is a rare phenomenon, occurring in about 10% of pituitary tumors, that seems to be associated with an aggressive phenotype, at least in thyrotroph adenomas. Further studies are required to confirm this association and to identify the genes, in addition to sst5, lost in these tumors.

Original languageEnglish
Pages (from-to)937-942
Number of pages6
JournalJournal of Endocrinological Investigation
Volume27
Issue number10
Publication statusPublished - Nov 2004

Keywords

  • Loss of heterozygosity
  • Somatotroph adenomas
  • SS receptor
  • sst5
  • Thyrotroph adenomas

ASJC Scopus subject areas

  • Endocrinology

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    Filopanti, M., Ballarè, E., Lania, A. G., Bondioni, S., Verga, U., Locatelli, M., Zavanone, L. M., Losa, M., Gelmini, S., Peri, A., Orlando, C., Beck-Peccoz, P., & Spada, A. (2004). Loss of heterozygosity at the SS receptor type 5 locus in human GH- and TSH-secreting pituitary adenomas. Journal of Endocrinological Investigation, 27(10), 937-942.