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Scientific article
Case report
Open access
English

The tumor suppressor gene TRC8/RNF139 is disrupted by a constitutional balanced translocation t(8;22)(q24.13;q11.21) in a young girl with dysgerminoma

Published inMolecular cancer, vol. 8, 52
Publication date2009
Abstract

BACKGROUND: RNF139/TRC8 is a potential tumor suppressor gene with similarity to PTCH, a tumor suppressor implicated in basal cell carcinomas and glioblastomas. TRC8 has the potential to act in a novel regulatory relationship linking the cholesterol/lipid biosynthetic pathway with cellular growth control and has been identified in families with hereditary renal (RCC) and thyroid cancers. Haploinsufficiency of TRC8 may facilitate development of clear cell-RCC in association with VHL mutations, and may increase risk for other tumor types. We report a paternally inherited balanced translocation t(8;22) in a proposita with dysgerminoma. METHODS: The translocation was characterized by FISH and the breakpoints cloned, sequenced, and compared. DNA isolated from normal and tumor cells was checked for abnormalities by array-CGH. Expression of genes TRC8 and TSN was tested both on dysgerminoma and in the proposita and her father. RESULTS: The breakpoints of the translocation are located within the LCR-B low copy repeat on chromosome 22q11.21, containing the palindromic AT-rich repeat (PATRR) involved in recurrent and non-recurrent translocations, and in an AT-rich sequence inside intron 1 of the TRC8 tumor-suppressor gene at 8q24.13. TRC8 was strongly underexpressed in the dysgerminoma. Translin is underexpressed in the dysgerminoma compared to normal ovary.TRC8 is a target of Translin (TSN), a posttranscriptional regulator of genes transcribed by the transcription factor CREM-tau in postmeiotic male germ cells. CONCLUSION: A role for TRC8 in dysgerminoma may relate to its interaction with Translin. We propose a model in which one copy of TRC8 is disrupted by a palindrome-mediated translocation followed by complete loss of expression through suppression, possibly mediated by miRNA.

Keywords
  • Child
  • Chromosome Mapping
  • Chromosomes, Human, Pair 22
  • Chromosomes, Human, Pair 8
  • DNA-Binding Proteins/genetics/metabolism
  • Dysgerminoma/genetics/metabolism/pathology
  • Female
  • Gene Expression Regulation, Neoplastic
  • Genes, Tumor Suppressor
  • Genetic Predisposition to Disease
  • Humans
  • Immunohistochemistry
  • Lymphocytes/ultrastructure
  • Male
  • Ovarian Neoplasms/genetics/metabolism/surgery
  • Ovary/pathology
  • Receptors, Cell Surface/genetics/metabolism
  • Translocation, Genetic
  • Von Hippel-Lindau Tumor Suppressor Protein/genetics/metabolism
Citation (ISO format)
GIMELLI, Stefania et al. The tumor suppressor gene TRC8/RNF139 is disrupted by a constitutional balanced translocation t(8;22)(q24.13;q11.21) in a young girl with dysgerminoma. In: Molecular cancer, 2009, vol. 8, p. 52. doi: 10.1186/1476-4598-8-52
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Article (Published version)
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Identifiers
ISSN of the journal1476-4598
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