Elevated frequency of loss of heterozygosity in mammary tumors arising in mouse mammary tumor virus/neu transgenic mice

• Published in: Cancer research (Chicago, Ill.) Vol. 59; no. 10; pp. 2438 - 2444
• Main Authors: COOL, M, JOLICOEUR, P
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15.05.1999
• Subjects: Acyltransferases; Alleles; Animal tumors. Experimental tumors; Animals; Biological and medical sciences; Cadherins - genetics; Chromosome Mapping; Crosses, Genetic; Experimental genital and mammary tumors; Female; Gene Deletion; Genes, erbB-2; Genes, p16; Genes, Tumor Suppressor; Loss of Heterozygosity; Male; Mammary Neoplasms, Experimental - genetics; Mammary Tumor Virus, Mouse - genetics; Medical sciences; Membrane Proteins - genetics; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Transgenic; Mouse mammary tumor virus; Tumors; Chromosomal aberration; Genetic mapping; Animal model; Tumoral tissue; Rodentia; Retroviridae; Transgenic animal; Malignant tumor; Mammalian type B retrovirus; Virus; Mammary gland diseases; Abnormal chromosome F19; Vertebrata; Abnormal chromosome C8; Mammalia; Mouse; Abnormal chromosome B4; C-Onc gene; Loss of heterozygosity; Abnormal chromosome; Genetics; Mammary gland; Mouse mammary tumor virus; Tumor suppressor gene
• ISSN: 0008-5472; 1538-7445

Loss of heterozygosity (LOH) analysis was performed on 62 mammary tumors that were induced in (BALB/c x C57BL/6)F1 mouse mammary tumor virus/neu transgenic mice. Eighty-six simple sequence length polymorphism markers were used to cover all of the somatic chromosomes. Frequency of LOH was observed to be significant for chromosomes 4 (50%), 19 (32%), and 8 (21%). On chromosome 4, at least three distinct regions of allelic deletions could be identified: one proximal to 22 cM; the second close to the p16INK4a/p15INK4b locus, which is commonly deleted in various tumors; and the third one in the proximity of Mom1. The frequency of LOH on chromosome 19 was the same for the four markers used. Our data suggested the presence of two distinct LOH loci, one proximal to 47 cM and the other at the distal region. On chromosome 8, possibly two distinct LOH loci could be recognized, one around 52 cM and the other one at 67 cM or distal to it. These regions map close to E-cadherin (Cdh1) and M-cadherin (Cdh15) loci, respectively. Because LOH sites are thought to harbor tumor suppressor genes, this allelotype screening has allowed the mapping of putative tumor suppressor genes that may be implicated, in collaboration with the erbB-2/neu oncogene, in the development of mammary tumors in these transgenic mice.