THE PLASMACYTOMA RESISTANCE GENE, PCTR2, DELAYS THE ONSET OF TUMORIGENESIS AND RESIDES IN THE TELOMERIC REGION OF CHROMOSOME-4

Mouse plasmacytomas share pathogenetic features in common with both mu ltiple myeloma and Burkitt's lymphoma in humans. Susceptibility to pla smacytoma induction by intraperitoneal pristane in mice is controlled by multiple genes. At least two of these genes reside on mouse chromos ome 4 in regions of the genome sharing linkage homology with human chr omosomes 9p21, 1p32. and 1p36. A series of congenic strains recombinan t for regions of mouse chromosome 4 in the vicinity of the Pctr2 predi sposition locus were created and typed for their tumor susceptibility/ resistance-phenotypes, These strains were derived by introgressively b ackcrossing alleles from resistant DBA/2 mice onto the susceptible BAL B/cAnPt background. Six resistant and two susceptible strains were all elotyped for 10 genes and 49 random DNA markers to identify the smalle st region of overlap in the resistant strains. These studies have dete rmined that the Pctr2 locus resides in either a 500-kb interval proxim al to Nppa, or in a 1- to 2-centiMorgan (cM) interval distal to Nppa. In these congenic strain analyses, the Nppa and Fv1 loci, in addition to genes within about 1 cM of these loci, have been excluded as candid ates for the Pctr2 locus. A relevant locus that may reside in this int erval is Rep2; it is associated with the efficiency of repairing X-ray induced DNA damage sustained during the G2 phase of the mitotic cycle . The Pctr2 locus acts in a codominant fashion. F1 hybrids between res istant and susceptible congenic strains exhibit a reduced tumor incide nce and a significant delay in the onset of tumorigenesis. Identificat ion and eventual cloning of the Pctr2 locus may assist in the identifi cation of genes involved in many types of cancer showing aberrations i n human chromosome 1p36. (C) 1997 by The American Society of Hematolog y.