Identification of the von Hippel-Lindau disease tumor suppressor gene

Journal Article · Fri May 28 00:00:00 EDT 1993 · Science (Washington, D.C.); (United States)

DOI:https://doi.org/10.1126/science.8493574· OSTI ID:6310456

Latif, F; Yao, Masahiro; Orcutt, L; Kuzmin, I; Zhou, Fangwei; Zbar, B; Lerman, M I; Dean, M ^[1]; Tory, K; Duh, Fuhmei; Stackhouse, T; Modi, W; Geil, L; Schmidt, L; Li, Hua; Wei, Ming Hui; Chen, Fan; Glavac, D ^[2]; Gnarra, J; Walther, M M ; Weng, Yongkai; Duan, D S.R.; Linehan, W M; Glenn, G; Choyke, P ^[3]; Richards, F M; Crossey, P A; Ferguson-Smith, M A; Maher, E R ^[4]; Le, Paslier D; Chumakov, I; Cohen, D ^[5]; Chinault, A C ^[6]

---

1. National Cancer Inst., Frederick, MD (United States)
2. Program Resources, Inc./DynCorp, Frederick, MD (United States) National Cancer Inst., Frederick, MD (United States)
3. National Cancer Inst., Bethesda, MD (United States)
4. Cambridge Univ. (United Kingdom)
5. Centre d'Etude du Polymorphisme Humain, Paris (France)
6. Baylor College, Houston, TX (United States)

A gene discovered by positional cloning has been identified as the von Hippel-Lindau (VHL) disease tumor suppressor gene. A restriction fragment encompassing the gene showed rearrangements in 28 of 221 VHL kindreds. Eighteen of these rearrangements were due to deletions in the candidate gene, including three large nonoverlapping deletions. Intragenic mutations were detected in cell lines derived from VHL patients and from sporadic renal cell carcinomas. The VHL gene is evolutionarily conserved and encodes two widely expressed transcripts of approximately 6 and 6.5 kilobases. The partial sequence of the inferred gene product shows no homology to other proteins, except for an acidic repeat domain found in the procyclic surface membrane glycoprotein of Trypanosoma brucei. 17 refs., 4 figs. 1 tab.

• OSTI ID: 6310456
• Journal Information: Science (Washington, D.C.); (United States), Vol. 260:5112; ISSN 0036-8075
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
CENTRAL NERVOUS SYSTEM
NEOPLASMS
HUMAN CHROMOSOME 3
MAPPING
KIDNEYS
GENES
INHIBITION
AMINO ACID SEQUENCE
ANGIOMAS
BRAIN
CYSTS
DNA-CLONING
GENE MUTATIONS
MEMBRANE PROTEINS
PANCREAS
SPINAL CORD
BODY
CARCINOMAS
CHROMOSOMES
CLONING
DIGESTIVE SYSTEM
DISEASES
DNA HYBRIDIZATION
ENDOCRINE GLANDS
GLANDS
HUMAN CHROMOSOMES
HYBRIDIZATION
MOLECULAR STRUCTURE
MUTATIONS
NERVOUS SYSTEM
ORGANIC COMPOUNDS
ORGANS
PATHOLOGICAL CHANGES
PROTEINS
550400* - Genetics