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PMID: 9689122 Published · ppublish English Journal Article Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

The hereditary renal cell carcinoma 3;8 translocation fuses FHIT to a patched-related gene, TRC8.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 95 ·No. 16 ·1998-08-04 ·Pages 9572-7

Gemmill RM, West JD, Boldog F, Tanaka N, Robinson LJ, Smith DI, Li F, Drabkin HA

Abstract

The 3;8 chromosomal translocation, t(3;8)(p14.2;q24.1), was described in a family with classical features of hereditary renal cell carcinoma. Previous studies demonstrated that the 3p14.2 breakpoint interrupts the fragile histidine triad gene (FHIT) in its 5' noncoding region. However, evidence that FHIT is causally related to renal or other malignancies is controversial. We now show that the 8q24.1 breakpoint region encodes a 664-aa multiple membrane spanning protein, TRC8, with similarity to the hereditary basal cell carcinoma/segment polarity gene, patched. This similarity involves two regions of patched, the putative sterol-sensing domain and the second extracellular loop that participates in the binding of sonic hedgehog. In the 3;8 translocation, TRC8 is fused to FHIT and is disrupted within the sterol-sensing domain. In contrast, the FHIT coding region is maintained and expressed. In a series of sporadic renal carcinomas, an acquired TRC8 mutation was identified. By analogy to patched, TRC8 might function as a signaling receptor and other pathway members, to be defined, are mutation candidates in malignant diseases involving the kidney and thyroid.

MeSH Terms
Acid Anhydride Hydrolases Amino Acid Sequence Base Sequence Carcinoma, Renal Cell/genetics,pathology Chromosome Mapping Chromosomes, Human, Pair 3 Chromosomes, Human, Pair 8 DNA Primers Humans Kidney Neoplasms/genetics,pathology Membrane Proteins/chemistry,genetics Molecular Sequence Data Neoplasm Proteins/genetics Proteins/genetics Receptors, Cell Surface Sequence Homology, Amino Acid Translocation, Genetic Tumor Cells, Cultured
Chemicals
DNA Primers Membrane Proteins Neoplasm Proteins Proteins RNF139 protein, human Receptors, Cell Surface fragile histidine triad protein Acid Anhydride Hydrolases
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Gemmill R M
Division of Medical Oncology, University of Colorado Health Sciences Center, 4200 East 9th Avenue, Denver, CO 80262, USA. [email protected]
West J D
Boldog F
Tanaka N
Robinson L J
Smith D I
Li F
Drabkin H A
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.95.16.9572
Email
[email protected]
Published
1998-08-04
Pages
9572-7
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC21380
Subset
IM
Grants
NCI NIH HHS · CA58187 · United States
Databases
GENBANK
AF064800, AF064801
External Links
PubMed source DOI: 10.1073/pnas.95.16.9572 PMC Full Text View journal details
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