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Publication : Allele-specific loss or imbalance of chromosomes 9, 15, and 16 in B-cell tumors from interspecific F1 hybrid mice carrying Emu-c-myc or N-myc transgenes.

First Author  Linardopoulos S Year  2000
Journal  Int J Cancer Volume  88
Issue  6 Pages  920-7
PubMed ID  11093815 Mgi Jnum  J:66124
Mgi Id  MGI:1928007 Doi  10.1002/1097-0215(20001215)88:6<920::aid-ijc13>3.0.co;2-#
Citation  Linardopoulos S, et al. (2000) Allele-specific loss or imbalance of chromosomes 9, 15, and 16 in B-cell tumors from interspecific F1 hybrid mice carrying e&mgr;-c-myc or N-myc transgenes. Int J Cancer 88(6):920-7
abstractText  Mice carrying an immunoglobulin enhancer (E&mgr;-) linked c- or N-myc transgene develop fatal monoclonal or oligoclonal pre-B or B-cell lymphomas. This indicates that, beside the E&mgr;-activated myc gene, additional genetic changes are required for tumor development. To trace these additional changes, we carried out a genome-wide search for loss of heterozygosity (LOH) and allelic imbalance (AI). 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 plasmacytomas from non-transgenic F1 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 in N-myc F1 mice. No LOH-9 was found in any of the 11 lymphomas from E&mgr;-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 spretus chromosome 9 confers resistance to the development of N-myc but not c-myc-induced lymphomas. AI of chromosome 15 markers (AI-15) was detected in 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 and plasmacytomas with AI-15 revealed a relative gain of the spretus-derived D15Mit6 allele (located at 13.7 cM from the centromere), together with a gain of the BALB/c allele of the more distal (29.6 cM) D15Mit64 marker, suggesting somatic recombination. LOH in the region close to c-myc was detected in a proportion of tumors with AI-15. The observation of complex genetic alterations includes somatic recombination, AI and LOH involving chromosome 15 in tumors induced by a myc transgene. This indicates that at least two genes in addition to c-myc on this chromosome can be involved in lymphoma development. Copyright 2000 Wiley-Liss, Inc.
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