Analysis of loss of heterozygosity in lymphoma and leukaemia arising in F1hybrid mice locates a common region of chromosome 4 loss

Previous studies have identified five lymphoma-related tumour suppressor ge ne regions on murine chromosome 4. Using detailed allelotype analysis on a range of lympho-haematopoietic tumour types arising in F1 hybrid mice, we n ow show a consistent pattern of loss of heterozygosity (FOH) which identifi es a common region of loss delineated by microsatellites D4Mit21 and D4Mit5 3 on proximal chromosome 4. This critical segment corresponds to the thymic lymphoma tumour suppressor region 5 (TLSR5) identified in an earlier study . Tumours of this type have also been reported as showing allelic loss from the Trp53 and Ikoros regions on chromosome 11. In the present study, only a small fraction of tumours showed LOH in the Ikaros region, while a minori ty of lymphomas, but not acute myeloid leukaemias, showed allelic loss of t he chromosome 11 segment encoding Trp53. These and other data indicate stro ngly that the genomic regions identified as showing recurrent LOH depend on the genetic background of the mice. Overall, the results indicate a key ro le for a tumour suppressor gene(s) encoded in an similar to3 cM segment on proximal chromosome 4 and provide an experimental basis for the further inv estigation of the functional role of candidate genes which include Pox5 and Tgfbr1. (C) 2001 Wiley-Liss. Inc.