Physical mapping of a commonly deleted region, the site of a candidate tumor suppressor gene, at 12q22 in human male germ cell tumors
- Memorial Sloan-Kettering Cancer Center, New York, NY (United States); and others
A candidate tumor suppressor gene (TSG) site at 12q22 characterized by a high frequency of loss of heterozygosity (LOH) and a homozygous deletion has previously (LOH) and a homozygous deletion has previously been reported in human male germ cell tumors (GCTs). In a detailed deletion mapping analysis of 67 normal-tumor DNAs utilizing 20 polymorphic markers mapped to 12q22-q24, we identified the limits of the minimal region of deletion at 12q22 between D12S377 (priximal) and D12S296 (distal). We have constructed a YAC contig map of a 3-cM region of this band between the proximal marker D12S101 and the distal marker D12S346, which contained the minimal region of deletion in GCTs. The map is composed of 53 overlapping YACs and 3 cosmids onto which 25 polymorphic and nonpolymorphic sequence-tagged sites (STSs) were placed in a unique order. The size of the minimal region of deletion was approximately 2 Mb from overlapping, nonchimeric YACs that spanned the region. We also developed a radiation hybrid (RH) map of the region between D12S101 and D12S346 containing 17 loci. The consensus order developed by RH mapping is in good agreement with the YAC STS-content map order. The RH map estimated the distance between D12S101 and D12S346 to be 246 cR{sub 8000} and the minimal region of deletion to be 141 cR{sub 8000}. In addition, four genes that were previously mapped to 12q22 have been excluded as candidate genes. The leads gained from the deletion mapping and physical maps should expedite the isolation and characterization of the TSG at 12q22. 35 refs., 4 figs., 2 tabs.
- OSTI ID:
- 465993
- Journal Information:
- Genomics, Vol. 35, Issue 3; Other Information: PBD: 1 Aug 1996
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
BASIC STUDIES
GENES
GENETIC MAPPING
HUMAN CHROMOSOME 12
CHROMOSOMAL ABERRATIONS
DNA SEQUENCING
MUTATION FREQUENCY
GERM CELLS
NEOPLASMS
CONTIGS
DESIGN
POLYMERASE CHAIN REACTION
BIOLOGICAL MARKERS
RADIATION INDUCED MUTANTS
STATISTICS
ELECTROPHORESIS
FLUORESCENCE
IN-SITU HYBRIDIZATION
RFLPS