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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

Beri, Silvana
Drabkin, Harry A.
Gambini, Claudio
Gregorio, Andrea
Fiorio, Patrizia
Zuffardi, Orsetta
Gemmill, Robert M.
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Published in Molecular cancer. 2009, vol. 8, 52
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 ChildChromosome MappingChromosomes, Human, Pair 22Chromosomes, Human, Pair 8DNA-Binding Proteins/genetics/metabolismDysgerminoma/genetics/metabolism/pathologyFemaleGene Expression Regulation, NeoplasticGenes, Tumor SuppressorGenetic Predisposition to DiseaseHumansImmunohistochemistryLymphocytes/ultrastructureMaleOvarian Neoplasms/genetics/metabolism/surgeryOvary/pathologyReceptors, Cell Surface/genetics/metabolismTranslocation, GeneticVon Hippel-Lindau Tumor Suppressor Protein/genetics/metabolism
PMID: 19642973
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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 https://archive-ouverte.unige.ch/unige:5661

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Deposited on : 2010-03-30

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