A total of 429 g-ray-induced thymic lymphomas were obtained from F 1 and backcross mice between BALB/c and MSM strains, about a half of which carried a p53-de®cient allele. A genome-wide allelic loss analysis has revealed two loci exhibiting frequent allelic losses but no allelic preference, one is localized within a 2.9 cM region between D12Mit53 and D12Mit279 loci on chromosome 12, and the other is near the D16Mit122/D16Mit162 loci on chromosome 16. The frequency of allelic loss in the D12Mit279 region is 62% and does not dier in tumors between the presence and absence of the p53-de®cient allele. In contrast, the loss frequency of D16Mit122 is raised by the existence of p53-de®cient allele: 62% for p63(7/+) and 13% for p53(+/+), suggesting cooperative function of the two losses. The D12Mit279 and D16Mit122 regions probably harbor dierent types of tumor suppressor gene that play key roles in lymphoma development.
Our previous genome-wide analysis of allelic loss for thymic lymphomas that were induced by g-irradiation in F 1 hybrid mice between BALB/c and MSM strains suggested the centromeric region on chromosome 11 as a site harboring a tumor suppressor gene. Interestingly, to this region the mouse Ikaros gene was mapped which was postulated to participate in oncogenic process from the study of Ikaros knockout mice. Here we show ®ne allelic loss mapping in the vicinity of Ikaros in 191 lymphomas, indicating that the critical region of allelic loss was centered at the Ikaros locus. PCR analysis revealed that nine lymphomas failed to give PCR-ampli®cation for either of two exon primer pairs, indicative of homozygous deletion. Six and ®ve mutations were detected in the N-terminal zinc ®nger domain and the activation domain of Ikaros, respectively, and six of the eleven were frameshift or nonsense mutations that resulted in truncation of Ikaros protein. The results strongly suggest a direct role for Ikaros in development of mouse thymic lymphomas. This provides the experimental basis for further analysis of Ikaros mutations in human cancer.
Pneumatosis cystoides intestinalis (PCI) is knownto be a relatively rare condition which is characterized by gas cysts in the gastrointestinal mucosa. Wetreated four cases of PCI accompanied by hematological malignancies during chemotherapy treatment. All cases suffered from abdominal discomfort. Abdominal X-ray films revealed gas cysts in the intestine. PCI was observed during leukocytopenic states, and three cases had septicemia. Etoposide was administered to three cases, and prednisolone to all cases. It is considered that PCI sometimes occurs in patients with hematological malignancies during a period of leukocytopenia, and may be caused by intestinal mucosal damagedue to myelosuppressive agents and immunosuppressionfrom prednisolone. (Internal Medicine 34: 212-215, 1995)
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