SUBMICROSCOPIC DELETIONS OF 3P SEQUENCES IN PLEOMORPHIC ADENOMAS WITHT(38)(P21Q12)

A subgroup of benign pleomorphic adenomas of the salivary glands is ch aracterized by translocations, or on rare occasions deletions, with br eakpoints at 3p21. We have applied restriction fragment length polymor phism (RFLP) analysis to assess the frequency of allelic losses at fou r different loci located within 3p21-->p25 in 35 pleomorphic adenomas, 18 of which were also karyotyped. Parallel analysis of constitutional and tumor DNAs in informative tumors revealed that all patients retai ned heterozygosity in their rumor DNA at the D3S2 and RAF1 loci. Among the 29 tumors informative for THRB three showed loss of heterozygosit y (LOH). All three tumors had a t(3;8)(p21;q12). Of the 23 tumors info rmative for D3F 15S2, one showed LOH. This tumor also had a t(3;8)(p21 ;q12). To further map the deletions in relation to the 3p21 translocat ion breakpoint, we also sublocalized the THRB locus. Using in situ hyb ridization we assigned the gene to 3p24. 1-.3. The fact that none of t he tumors with loss of 3p alleles showed cytogenetic evidence of delet ions indicates that the losses are submicroscopic, probably interstiti al, and in most cases distal to the 3p21 breakpoint. This was confirme d in one case with loss of a THRB allele where both proximal (D3F 15S2 ) and distal (RAF1) markers retained heterozygosity. Our results sugge st that deletion of 3p sequences might be of progressional importance in a subset of pleomorphic adenomas with t(3;8)(p21;q12). Genes Chromo som Cancer 10:256-261 (1994). (C) 1994 Wiley-Liss, Inc.