Distinct structural abnormalities of chromosomes 11 and 12 associated with loss of heterozygosity in X-ray-induced mouse thymic lymphomas.
Loss of heterozygosity (LOH) plays an important role in leukemogenesis via inactivation of tumor suppressor genes. Recent studies have demonstrated that mouse thymic lymphomas (TL), a suitable model for the mechanistic study of human acute lymphoblastic leukemia, show frequent LOH on chromosomes 4 (p15/p16), 11 (Ikaros), 12 (Bcl11b), 19 (Pten), and X. To date, however, little data are available regarding the mechanism of LOH. In this study, we re-evaluated chromosomal abnormality and loss of heterozygosity in 26 TL-induced by x-rays in C57BL/6 (B6), C3H, and F1 (B6 x C3H) mice, using the quinacrine-Hoechst double-staining method and chromosome painting technique. Chromosomally abnormal cells were present in 25 TL examined (25/26, 96%). The most frequent abnormality was trisomy or partial trisomy of chromosome 15 (16/26, 62%), which is consistent with previous studies. Structural abnormalities of chromosome 11 with interstitial deletion of proximal region and chromosome 12 with translocation with deletion of distal region were newly identified in 7 (27%) and 12 (46%) cases, respectively. These results indicate that the distinct mechanism contributes to the LOH of each tumor suppressor gene on different chromosomal locations.
Yoshida
Mitsuaki A
MA
Biodosimetry Section, Department of Radiation Dosimetry, Research Center for Radiation Emergency Medicine, Anagawa, Inage-ku, Chiba 263-8555, Japan. myoshi@nirs.go.jp
Nakata
Akifumi
A
Akiyama
Miho
M
Kakinuma
Shizuko
S
Sado
Toshihiko
T
Nishimura
Mayumi
M
Shimada
Yoshiya
Y
D000818:Animals; D002869:Chromosome Aberrations; D020223:Chromosome Painting; D033481:Chromosomes, Mammalian; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D019656:Loss of Heterozygosity / Q000235:genetics*; D008223:Lymphoma / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D013953:Thymus Neoplasms / Q000235:genetics*; D014314:Trisomy; D014965:X-Rays