Radiation-associated loss of heterozygosity at the Znfn1a1 (Ikaros) locus on chromosome 11 in murine thymic lymphomas.
Although information on the molecular pathways in radiation carcinogenesis is accumulating, the data are still relatively scanty. To find the tumor suppressor locus associated with radiation carcinogenesis, we determined the frequency and distribution of loss of heterozygosity (LOH) of X-ray-induced thymic lymphomas of B6C3F(1) mice using 58 microsatellite markers and compared the results with those for spontaneous lymphomas and N-ethylnitrosourea (ENU)-induced lymphomas. Based on the results, we describe a unique locus with frequent LOH in the centromeric region of chromosome 11 of X-ray-induced lymphomas. This locus has never been observed to be altered similarly in either ENU-induced or spontaneous lymphomas, suggesting radiation-specific molecular alteration. The LOH patterns of individual thymic lymphomas indicated that the common region of LOH was located within 1.6 cM between D11Mit62 and D11Mit204, a region syntenic to human chromosome 7p13. Linkage analysis revealed that the markers of the common LOH region were genetically linked to Ikaros (now known as Znfn1a1), a master gene of lymphopoiesis. Although the presence of radiation-associated LOH in other loci cannot be ruled out, these results suggest a novel molecular pathway in induction of thymic lymphomas by ionizing radiation.
Shimada
Y
Y
Division of Low Dose Radiation and Experimental Carcinogenesis, National Institute of Radiological Sciences, Chiba 263-8555, Japan.
Nishimura
M
M
Kakinuma
S
S
Okumoto
M
M
Shiroishi
T
T
Clifton
K H
KH
Wakana
S
S
D000483:Alleles; D000818:Animals; D002273:Carcinogens; D002875:Chromosomes / Q000235:genetics / Q000528:radiation effects*; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D004268:DNA-Binding Proteins; D005038:Ethylnitrosourea; D005260:Female; D005796:Genes / Q000528:radiation effects*; D008040:Genetic Linkage; D006410:Hematopoiesis / Q000528:radiation effects; D006801:Humans; D051740:Ikaros Transcription Factor; D019656:Loss of Heterozygosity / Q000528:radiation effects*; D008223:Lymphoma / Q000139:chemically induced / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018895:Microsatellite Repeats; D009381:Neoplasms, Radiation-Induced / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D016133:Polymerase Chain Reaction; D013045:Species Specificity; D013953:Thymus Neoplasms / Q000139:chemically induced / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics*
D002273:Carcinogens; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; C497239:IKZF1 protein, human; D014157:Transcription Factors; C497238:Zfpn1a1 protein, mouse; D051740:Ikaros Transcription Factor; D005038:Ethylnitrosourea