YAC CONTIGS COVERING AN 8-MEGABASE REGION OF 3P DELETED IN THE SMALL-CELL LUNG-CANCER CELL-LINE U2020

Somatic deletions of chromosome 3p occur at high frequencies in cancer s of kidney, breast, cervix, head and neck, nasopharynx, and lung. The frequency of 3p deletion in lung cancer approaches 100% among small c ell. lesions and 70 to 80% in non-small cell lesions. This evidence st rongly implies that one or more tumor suppressor genes of potentially widespread significance reside within the deleted region(s). Precise d efinition of the deleted target region(s) has been difficult due to th e extensive area(s) lost and use of markers with low informativeness. However, improved definition remains essential to permit isolation of putative tumor suppressor genes from 3p. The identification of several small, homozygous 3p deletions in lung cancer cell lines has provided a critical resource that will assist this search. The U2020 cell line contains a small homozygous deletion that maps to a very proximal reg ion of 3p and includes the marker D3S3. We previously identified a sub set of DNA markers located within the deleted region and determined th eir relative order by pulsed-field gel mapping studies. In the present report, we describe the development of YAC contigs that span the majo rity of the deleted region and link up to flanking markers on both sid es. The centromere proximal portion of the contig crosses the breakpoi nt from an X;3 translocation located within 3p12 providing both locati on and orientation to the map. PCR-based (CA)(n) microsatellite polymo rphisms have been localized within and flanking the deletion region. T hese markers should greatly facilitate loss-of-heterozygosity studies of this region in human cancer. The contig provides a direct means for isolation of putative tumor suppressor genes from this segment of 3p. (C) 1995 Academic Press, Inc.