A 3-Mb High-Resolution BAC/PAC Contig of 12q22 Encompassing the 830-kb Consensus Minimal Deletion in Male Germ Cell Tumors

  1. Vundavalli V.V.S. Murty1,5,
  2. Kate Montgomery2,
  3. Shipra Dutta1,
  4. Shashi Bala1,
  5. Beatrice Renault2,
  6. George J. Bosl3,
  7. Raju Kucherlapati2, and
  8. Raju S.K. Chaganti4
  1. 1Department of Pathology, College of Physicians & Surgeons of Columbia University, New York, New York 10032 USA; 2Department of Molecular Genetics, Albert Einstein College of Medicine, Bronx, New York 10461 USA; 3Department of Medicine, and 4Laboratory of Cancer Genetics & Department of Human Genetics, Memorial Sloan-Kettering Cancer Center, New York, New York 10021 USA

Abstract

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 andD12S296, 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 ∼830 kb betweenD12S1716 (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. AQ254896AQ254955 andAQ269251AQ269266. Online supplementary material is available athttp://www.genome.org]

Footnotes

  • 5 Corresponding author.

  • E-MAIL vvm2{at}columbia.edu; FAX (212) 305-5498.

    • Received March 10, 1999.
    • Accepted May 18, 1999.
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