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Allele‐specific loss or imbalance of chromosomes 9, 15, and 16 in B‐cell tumors from interspecific F1 hybrid mice carrying eμ‐c‐ myc or N‐ myc transgenes
Author(s) -
Linardopoulos Spiros,
Silva Santiago,
Klein George,
Balmain Allan
Publication year - 2000
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/1097-0215(20001215)88:6<920::aid-ijc13>3.0.co;2-#
Subject(s) - biology , loss of heterozygosity , transgene , plasmacytoma , microbiology and biotechnology , chromosome , allele , gene , cancer research , genetics , immunology , multiple myeloma
Abstract Mice carrying an immunoglobulin enhancer (Eμ‐) linked c‐ or N‐ myc transgene develop fatal monoclonal or oligoclonal pre‐B or B‐cell lymphomas. This indicates that, beside the Eμ‐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 × 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 Eμ‐c‐ myc F1 mice and only in 1 of 46 (2%) tumors derived from non‐transgenic (BALB/c × 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. Int. J. Cancer 88:920–927, 2000. © 2000 Wiley‐Liss, Inc.