title: 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.
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.
  
  
  CONCLUSIONS
  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.
authors: Biologia Generale e Genetica Medica, Università di Pavia, Pavia, Italy. stefania.gimelli@gmail.com
authors: Stefania
authors: S
authors: Gimelli
authors: Silvana
authors: S
authors: Beri
authors: Harry A
authors: HA
authors: Drabkin
authors: Claudio
authors: C
authors: Gambini
authors: Andrea
authors: A
authors: Gregorio
authors: Patrizia
authors: P
authors: Fiorio
authors: Orsetta
authors: O
authors: Zuffardi
authors: Robert M
authors: RM
authors: Gemmill
authors: Roberto
authors: R
authors: Giorda
authors: Giorgio
authors: G
authors: Gimelli
mesh_terms: D002648:Child; D002874:Chromosome Mapping; D002892:Chromosomes, Human, Pair 22; D002898:Chromosomes, Human, Pair 8; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004407:Dysgerminoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry; D008214:Lymphocytes / Q000648:ultrastructure; D008297:Male; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000601:surgery; D010053:Ovary / Q000473:pathology; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000378:metabolism; D014178:Translocation, Genetic; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; C114025:RNF139 protein, human; D011956:Receptors, Cell Surface; C095563:TSN protein, human; D051794:Von Hippel-Lindau Tumor Suppressor Protein; C497446:VHL protein, human