Analysis of Allele Loss Regions in Chromosomes 9,10,12 in Radiation Mammary Carcinogenesis of Atm and p53 Heterozygous Deficient Mice

Abstract

To analyze putative tumor suppressor genes in mammary carcinogenesis, we refined the regions with frequent loss of heterozygosity(LOH) on chromosomes 9,10 and 12 in the tumors developed in p53 and Atm heterozygous deficient mice. F₁ females produced by BALB/cHeA-p53^+/KO and MSM/Ms-Atm^+/KO were exposed to 5Gy of X-rays at five weeks of age. DNA was extracted from mammary adenocarcinomas and analyzed for LOH in detail. We found frequent LOH in 2 regions on chromosome 12. One region is located near centromere. The frequency of LOH reached 60%. Allele derived from BALB/c was preferentially lost, suggesting a contribution of this region to cancer susceptibility. The other region includes D12Mit132(52cM), and frequency of LOH was about 56%. Frequent allele losses were also found in this region of lymphomas. Notable LOH was also observed at D9Mit20(60cM)(20%) and D10Mit7(43cM)(36%). However, wild allele of Atm on chromosome 9 was retained. [J Radiat Res 44:399 (2003)]