A 3-Mb high-resolution BAC/PAC contig of 12q22 encompassing the 830-kb consensus minimal deletion in male germ cell tumors.
Cytogenetic and molecular genetic analyses have shown that the 12q22 region is recurrently deleted in male germ cell tumors (GCTs), suggesting that this site may harbor a tumor suppressor gene (TSG). Previous loss of heterozygosity (LOH) analyses identified a consensus minimal deleted region between the markers D12S377 and D12S296, and a YAC clone contig covering the region was generated. Here, we describe a high-resolution sequence-ready physical map of this contig covering a 3-Mb region. The map comprised of 52 cosmids, 49 PACs, and 168 BACs that were anchored to the previous YAC contig; 99 polymorphic, nonpolymorphic, EST, and gene-based markers are now placed on this map in a unique order. Of these, 61 markers were isolated in the present study, including one that was polymorphic. In addition, we have narrowed the minimal deletion to approximately 830 kb between D12S1716 (proximal) and P382A8-AG (distal) by LOH analysis of 108 normal-tumor DNAs from GCT patients using 21 polymorphic STSs. These physical and deletion maps should prove useful for identification of the candidate TSG in GCTs, provide framework to generate complete DNA sequence, and ultimately generate a gene map of this segment of the chromosome 12. [The sequence data described in this paper have been submitted to the Genome Survey Sequence under accession nos. AQ254896-AQ254955 and AQ269251-AQ269266. Online supplementary material is available at http://www.genome.org]
Department of Pathology, College of Physicians & Surgeons of Columbia University, New York, New York 10032, USA. vvm2@columbia.edu
V V
VV
Murty
K
K
Montgomery
S
S
Dutta
S
S
Bala
B
B
Renault
G J
GJ
Bosl
R
R
Kucherlapati
R S
RS
Chaganti
D017101:Bacteriophage P1 / Q000235:genetics; D002876:Chromosomes, Bacterial / Q000235:genetics; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics*; D003001:Cloning, Molecular; D016384:Consensus Sequence; D020451:Contig Mapping; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics*; D020224:Expressed Sequence Tags; D005796:Genes / Q000235:genetics; D005819:Genetic Markers; D018237:Germinoma / Q000235:genetics*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D020161:Physical Chromosome Mapping; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion; D016324:Sequence Tagged Sites; D013736:Testicular Neoplasms / Q000235:genetics*
D004273:DNA, Neoplasm; D005819:Genetic Markers