Abstract
The p53 gene is a nuclear phosphoprotein that can function as a tumor suppressor gene (Michalovitz et al. 1991). Frequent mutations of the p53 gene have been detected in several types of solid tumors including breast (Mackay et al. 1988), colon (Vogelstein et al. 1989), lung (Yokota et al. 1987), liver carcinoma (Hsu et al. 1991), astrocytoma (Fults et al. 1992), and gliomas (Frankel et al. 1992). In the majority of these tumors with p53 mutations, allelic loss of one copy of human chromosome 17p, the site of the p53 gene has been demonstrated. Such allelic deletion has often been shown to be associated with point mutation on the remaining allele of the p53 gene (for review see Levine et al. 1991). For hematologic malignancies, several reports have demonstrated structural alterations and point mutations of the p53 gene in blast crisis of chronic myelogenous leukemia (CML) (Feinstein et al. 1991) and in acute myeloid leukemia (AML) (Fenaux et al. 1991). In the case of T- and B-cell lymphoid malignancies, a high incidence of p53 mutation was found to be associated with Burkitt lymphoma, B-cell chronic lymphocytic leukemia (B-CLL) but not in other B-cell (Gaidano et al. 1991) or T-cell malignancies (Jonveaux et al. 1991). We have studied the role of the p53 gene in murine lymphoid tumors (Brathwaite et al. 1992) as well as some human astrocytomas (Frankel et al. 1992 and Lang et al. 1992). We describe in this report the analysis of p53 mutations in 92 patients diagnosed with B-cell CLL. We also compared the frequency of point mutations with that of the loss of heterozygosity for chromosome 17p in the same group of patients.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsPreview
Unable to display preview. Download preview PDF.
References
Brathwaite O, Bayona W, Newcomb E (1992) p53 mutations in C57BL/6J murine thymic lymphomas induced by γ-irradiation and N-methylnitrosourea. Cancer Res 52: in press.
Feinstein E, Cimino G, Gale RP, Alimena G, Berthier R, Kishi K, Goldman J, Zaccaria A, Berrebi A, Canaani E (1991) p53 in chronic myelogenous leukemia in acute phase. Proc Natl Acad Sci. USA 88:6293–6297.
Fenaux P, Jonveaux P, Quiquandon I, Laï L, Pignon JM, Loueheux-Lefebvre MH, Bauters F, Berger R, Kerckaert JP (1991) p53 gene mutations in acute myeloid leukemia with 17p monosomy. Blood 78:1652–1657.
Frankel RH, Bayona W, Koslow M, Newcomb EW (1992) p53 mutations in human malignant gliomas: comparison of loss of heterozygosity with mutation frequency. Cancer Res 52:1427–1433.
Fults D, Brockmeyer D, Tullous MW, Pedone A, Cawthon RM (1992) p53 mutation and loss of heterozygosity on chromosomes 17 and 10 during human astrocytoma progression. Cancer Res 52:674–679.
Gaidano G, Ballerini P, Gong JZ, Inghirami G, Neri A, Newcomb EW, Magrath IT, Knowles DM, Dalla-Favera R (1991) p53 mutations in human lymphoid malignancies: association with Burkitt lymphoma and chronic lymphocytic leukemia. Proc Natl Acad Sci. USA 88:5413–5417.
Hsu LC, Metcalf RA, Sun T, Welsh A, Wang NJ, Harris CC (1991) Mutational hotspot in the p53 gene in human hepatocellular carcinomas. Nature 350:427–428.
Jonveaux P, Berger R (1991) Infrequent mutations in the p53 gene in primary human T-cell acute lymphoblastic leukemia. Leukemia 5:839–840.
Lang FF, Frankel RH, Bayona W, Koslow M, Miller DC, Newcomb EW (1992) Comparison of p53 mutations and loss of heterozygosity of chromosomes 17p and 10 in low grade and high grade human astrocytomas. Cancer Res: Submitted.
Levine AJ, Momand J, Finlay CA (1991) The p53 tumour suppressor gene. Nature 351:453–456.
Mackay J, Elder PA, Steel CM, Forrest AM, Evans HJ (1988) Allele loss on short arm of chromosome 17 in breast cancers. The Lancet 2:1384–1385.
Michalovitz D, Halevy O, Oren M (1991) p53 mutations: gains or losses? J Cell Biochem 45:22–29.
Vogelstein B, Fearon ER, Kern SE, Hamilton R, Preisinger AC, Nakamura Y, White R (1989) Allelotype of colorectal carcinomas. Science 244:207–211.
Yokota J, Wada M, Shimosato Y, Terada M, Sugimura T (1987) Loss of heterozygosity on chromosomes 3, 13, and 17 in small-cell carcinoma and on chromosome 3 in adenocarcinoma of the lung. Proc Natl Acad Sci. USA 84:9252–9256.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1992 Springer-Verlag Berlin Heidelberg
About this chapter
Cite this chapter
Rouby, S.E., Bayona, W., Pisharody, S.M., Newcomb, E.W. (1992). p53 Mutations in B-Cell Chronic Lymphocytic Leukemia. In: Potter, M., Melchers, F. (eds) Mechanisms in B-Cell Neoplasia 1992. Current Topics in Microbiology and Immunology, vol 182. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-77633-5_39
Download citation
DOI: https://doi.org/10.1007/978-3-642-77633-5_39
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-77635-9
Online ISBN: 978-3-642-77633-5
eBook Packages: Springer Book Archive