Positional cloning of the hereditary renal carcinoma 3;8 chromosome translocation breakpoint.
The chromosome (p14.2;q24.1) translocation t(3;8) has been associated with hereditary renal cancer in one family. Based on cytogenetic analyses 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 sensitive 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. We 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.
Boldog
F L
FL
University of Colorado Cancer Center, Division of Medical Oncology, Denver 80262.
Gemmill
R M
RM
Wilke
C M
CM
Glover
T W
TW
Nilsson
A S
AS
Chandrasekharappa
S C
SC
Brown
R S
RS
Li
F P
FP
Drabkin
H A
HA
D000818:Animals; D015152:Blotting, Northern; D002460:Cell Line; D002869:Chromosome Aberrations; D002874:Chromosome Mapping; D002893:Chromosomes, Human, Pair 3; D002898:Chromosomes, Human, Pair 8; D002999:Clone Cells; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D015342:DNA Probes; D015723:Gene Library; D006801:Humans; D006822:Hybrid Cells; D007668:Kidney; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D014178:Translocation, Genetic; D001749:Urinary Bladder Neoplasms / Q000235:genetics*
D015342:DNA Probes; D012313:RNA; D004247:DNA