Absolute genetic differences between neoplastic and nonneoplastic cell
s can be discerned at sites of homozygous deletions, These deletions a
re of critical interest because they might be useful in the identifica
tion of defective biochemical pathways in neoplastic cells, and subseq
uently for the development of new treatment strategies in human cancer
. We identified an area at 18q21.1 involved by homozygous deletions in
30% of pancreatic carcinomas, To characterize the homozygous deletion
s, we constructed a detailed physical map of nearly 2 Mb, containing y
east artificial chromosomes, P1-derived artificial chromosomes, cosmid
s and 24 sequence-tagged sites, The homozygously deleted area containe
d a new candidate tumor-suppressor gene (DPC4). To date, 23 (64%) of 3
5 pancreatic carcinomas carry at least one homozygous deletion at a pu
blished locus, The study of the total gene content of these loci, faci
litated by the sequence-tagged site markers and maps of these regions,
should help to reveal the absolute biochemical differences between ne
oplastic and nonneoplastic cells for a common human tumor.