A GROUP OF NOTI JUMPING AND LINKING CLONES COVER 2.5 MB IN THE 3P21-P22 REGION SUSPECTED TO CONTAIN A TUMOR-SUPPRESSOR GENE

The chromosomal region 3p21.2-p22 has been shown to be involved in the development of several forms of solid tumors. Such deletions, translo cations, and rearrangements presumably result in the disturbance or lo ss of a critical gene function. Pulsed-field gel electrophoresis (PFGE ), using NotI linking clones as a probe represent a powerful tool for analyzing such rearrangements. A NotI linking clone, AP20 (D3S1641), w as localized by in situ hybridization to 3p21.3-p22. Two NotI jumping clones adjacent to this clone were isolated, clone J32-612 covering 0. 5 Mb and clone J31-611 covering approximately 1 Mb. Clone J31-611 cros ses the border of the deletion present in hybrid cell line MCH939.2, w hich contains a deleted 3p21 region. For these jumping clones, corresp onding NotI linking clones, NLJ3 (D3S1642) and NL3-003, were isolated. Altogether, Linking and jumping clones from the AP20 locus hybridize to NotI fragments totaling 2.5 Mb in length. These NotI-containing clo nes defect expressed sequences in several human tissues. Clone NLJ3 po ssesses homology to the human platelet-derived endothelial cell growth factor gene and may represent a new member of this gene family Anothe r done (AP20) revealed 66% sequence similarity to rat skeletal muscle voltage-sensitive sodium channel subtype 2. Therefore, this group of c lones will be useful not only for analyzing rearrangements in tumors, but also for the isolation of new genes from the 3p21.3-p22 region.