Allele-specific loss or imbalance of chromosomes 9, 15, and 16 in B-cell tumors from interspecific F1 hybrid mice carrying E mu-C-myc or N-myc transgenes

Nice carrying an immunoglobulin enhancer (E mu-) linked cor N-myc transgene develop fatal monoclonal or oligoclonal pre-B or B-cell lymphomas, This in dicates that, beside the E mu -activated myc gene, additional genetic chang es are required for tumor development, To trace these additional changes, w e carried out a genome-wide search for loss of heterozygosity (LOH) and all elic imbalance (A1), This was done at 53 microsatellite markers in a panel of 34 lymphomas and four plasmacytomas from c- or N-myc transgene carrying (BALB/c x Mus spretus)F1 hybrids, An additional 43 lymphomas and three plas macytomas from non-transgenic pi mice were also investigated, Losses of one or more spretus-derived chromosome 9 markers were detected in 19 of 23 (83 %) of the lymphomas, but in none of the four plasmacytomas that developed i n N-myc F1 mice. No LOH-9 was found in any of the I I lymphomas from E mu - c-myc F1 mice and only in 1 of 46 (2%) tumors derived from non-transgenic ( BALB/c x spretus)F1 hybrid controls, These results suggest that a gene on s pretus chromosome 9 confers resistance to the development of N-myc but not c-myc-induced lymphomas, A1 of chromosome 15 markers (A1-15) was detected i n 57 of 77 (74%) lymphomas and in 5 of 7 (72%) plasmacytomas, independently of the transgenic status and the mode of induction. All of the lymphomas a nd plasmacytomas with A1-15 revealed a relative gain of the spretus-derived D15Mit6 allele (located at 13.7 cM from the centromere), together with a g ain of the BALB/c allele of the more distal (29.6 cM) D15Mit64 marker, sugg esting somatic recombination, LOH in the region close to c-myc was detected in a proportion of tumors with A1-15, The observation of complex genetic a lterations includes somatic recombination, Al and LOH involving chromosome 15 in tumors induced by a myc transgene, This indicates that at least two g enes in addition to c-myc on this chromosome can be involved in lymphoma de velopment. Int. J, Cancer 88: 920-927, 2000, (C) 2000 Wiley-Liss, Inc.