Positional cloning of the hereditary renal carcinoma 3; 8 chromosome translocation breakpoint

Journal Article · Wed Sep 15 00:00:00 EDT 1993 · Proceedings of the National Academy of Sciences of the United States of America; (United States)

DOI:https://doi.org/10.1073/pnas.90.18.8509· OSTI ID:5031413

Boldog, F L; Nilsson, A S; Drabkin, H A ^[1]; Gemmill, R M ^[2]; Wilke, C M; Glover, T W; Chandrasekharappa, S C ^[3]; Brown, R S ^[4]; Li, F P ^[5]

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1. Univ. of Colorado Cancer Center, Denver, CO (United States)
2. Eleanor Roosevelt Institute, Denver, CO (United States)
3. Univ. of Michigan, Ann Arbor, MI (United States)
4. Harvard Medical School, Boston, MA (United States)
5. Dana-Farber Cancer Institute, Boston, MA (United States)

The chromosome (p14.2;q24.1) translocation t(3;8) has been associated with hereditary renal cancer in one family. Based on cytogenetic analysis and loss-of-heterozygosity experiments, the 3p14 region has been independently implicated as harboring a tumor suppressor gene critical to kidney and lung cancer development. The 3p14.2 region also contains FRA3B, the most sensititive fragile site induced by aphidicolin. A chromosome 3 probe, R7K145, derived from a radiation-reduced hybrid was positioned between the t(3;8) breakpoint and an aphidicolin-induced 3p14 breakpoint. A yeast artificial chromosome (YAC) contig containing R7K145 was developed that crossed the aphidicolin-induced breakpoint on its telomeric side. A subsequent chromosome walk identified a YAC that crossed the 3;8 translocation breakpoint. A [lambda] sublibrary allowed isolation of clones spanning the rearrangement. Unique and evolutionarily conserved DNA sequences were used to screen a kidney cDNA library. The authors have identified a gene, referred to as HRCA1 (hereditary renal cancer associated 1), that maps immediately adjacent to the breakpoint. On the basis of its chromosomal position, HRCA1 may be a candidate tumor suppressor gene. 42 refs., 5 figs.

• OSTI ID: 5031413
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (United States), Vol. 90:18; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
HUMAN CHROMOSOME 3
GENETIC MAPPING
KIDNEYS
HEREDITARY DISEASES
NEOPLASMS
CHROMOSOME BREAKAGE
DNA-CLONING
HUMAN CHROMOSOME 8
BODY
CHROMOSOMAL ABERRATIONS
CHROMOSOMES
CLONING
DISEASES
DNA HYBRIDIZATION
HUMAN CHROMOSOMES
HYBRIDIZATION
MAPPING
MUTATIONS
ORGANS
550400* - Genetics