PHYSICAL MAPPING OF CHROMOSOME 17P13.3 IN THE REGION OF A PUTATIVE TUMOR-SUPPRESSOR GENE IMPORTANT IN MEDULLOBLASTOMA

Deletion mapping of a medulloblastoma tumor panel revealed loss of dis tal chromosome 17p13.3 sequences in tumors from 14 of 32 patients (44% ). Of the 14 tumors showing loss of heterozygosity by restriction frag ment length polymorphism analysis, 14 of 14 (100%) displayed loss of t he telomeric marker p144-D6 (D17S34), while a probe for the ABR gene o n 17p13.3 was lost in 7 of 8 (88%) informative cases. Using pulsed-hel d gel electrophoresis, we localized the polymorphic marker (VNTR-A) of the ABR gene locus to within 220 kb of the p144-D6 locus. A cosmid co ntig constructed in this region was used to demonstrate by fluorescenc e in situ hybridization that the ABR gene is oriented transcriptionall y 5' to 3' toward the telomere. This report provides new physical mapp ing data for the ABR gene, which has not been previously shown to be d eleted in medulloblastoma. These results provide further evidence for the existence of a second tumor suppressor gene distinct from p53 on d istal chromosome 17p. (C) 1994 Academic Press, Inc.