Abstract
The p16INK4a (α and β form) and p15INK4b genes were analysed for homozygous deletion, hypermethylation and point mutation in B6C3F1 mouse lymphomas induced by 2′,3′-dideoxycytidine or 1,3-butadiene. Although the p16INK4a-α gene appeared normal in DNA from 2′,3′-dideoxycytidine-induced lymphomas, Southern analyses revealed homozygous deletions or rearrangements of the p16INK4aβ and/or p15INK4b genes in four of 16 tumours. Surprisingly, two of these lymphomas showed exclusive deletions of the p16INK4a EIβ exon. The p15INK4b promoter region was hypermethylated in two additional 2′,3′-dideoxycytidine-induced lymphomas. In contrast, homozygous deletions spanning the p16INK4a and p15INK4b loci were observed in only two of 31 1,3-butadiene-induced tumours. Thus, these cyclin dependent kinase inhibitor genes may play a significant role in chemically induced mouse lymphomas and support the contention of tumour suppressor activity for the p19ARF protein encoded by the p16INK4a-β gene. Different genetic pathways may be involved in the development of these chemically induced tumours since we have previously shown that mutations in p53 and ras genes are common in 1,3-butadiene- but not 2′,3′-dideoxycytidine-induced lymphomas.
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Zhuang, SM., Schippert, Å., Haugen-Strano, A. et al. Inactivations of p16INK4a-α, p16INK4a-β and p15INK4b genes in 2′, 3′-dideoxycytidine- and 1,3-butadiene-induced murine lymphomas. Oncogene 16, 803–808 (1998). https://doi.org/10.1038/sj.onc.1201600
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DOI: https://doi.org/10.1038/sj.onc.1201600
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