Abstract
TP53 mutations are the most common genetic alterations in human malignancies. Since it was first discovered in 1989, more than 1700 different TP53 mutations have been described at more than 310 distinct resides. According to the most recent updated (September 2002) TP53 mutation database (http://www.iarc.fr/p53), more than 17,689 somatic mutations and 225 germline mutations have been reported (1). Detection of TP53 mutations have the following implications: (1) TP53 mutations cause inactivation of p53 protein, (2) different TP53 mutations are associated with different mechanisms causing the mutation, spontaneous mutations versus chemical carcinogen-induced mutations, and (3) TP53 mutations have been correlated with clinical stage and patient survival and are considered a potential prognostic indicator in some cancers. TP53 is a sensor of genomic stress and is involved in cell cycle control, angiogenesis, apoptosis, and DNA repair pathways. Therefore, detection of TP53 mutations can provide a basis for understanding interactions of other genes with p53.
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References
Olivier, M., Eeles, R., Hollstein, M., et al. (2002) The IARC TP53 database: new online mutation analysis and recommendations to users. Hum. Mutat. 19(6), 607–614.
Cotton, R. (1997) Slowly but surely towards better scanning for mutations. Trends Genet. 13, 43–46.
Southern, E. M. (1996) DNA Chips: analysing sequence by hybridization to oligonucleotides on a large scale. Trends Genet. 12, 110–115.
Wallace, R. (1997) DNA on a chip∶serving up the genome for diagnostics and research. Mol. Med. Today 3, 384–389.
Lipshutz, R., Fodor, S., Gingeras, T., et al. (1999) High density synthetic oligonucleotide arrays. Nature Genet. 21(Suppl.), 20–24.
Wen, W.-H., Bernstein, L., Lescallett, J., et al. (2000) Comparison of TP53 mutations identified by oligonucleotide microarray and conventional DNA sequence analysis. Cancer Res. 60, 2716–2722.
Ahrendt, S., Halachmi, S., Chow, J., et al. (1999) Rapid p53 sequence analysis in primary lung cancer using an oligonucleotide probe array. Proc. Natl. Acad. Sci. USA 96, 7382–7387.
Lu, M., Wikman, F., Orntoft, T., et al. (2002) Impact of alterations affecting the p53 pathway in bladder cancer on clinical outcome, assessed by conventional and array-based methods. Clin. Cancer Res. 8(1), 171–179.
Tonisson, N., Zernant, J., Kurg, A., et al. (2002) Evaluating the arrayed primer extension resequencing assay of TP53 tumor suppressor gene. Proc. Natl. Acad. Sci. USA 99(8), 5503–5508.
Shumaker, J., Tollet, J., Filbin, K., et al. (2001) APEX disease gene resequencing: mutations in exon 7 of the p53 tumor suppressor gene. Bioorg. Med. Chem. 9(9), 2269–2278.
Favis, R. and Barany, F. (2000) Mutation detection in K-ras, BRCA1, BRCA2, and p53 using PCR/LDR and a universal DNA microarray. Ann. NY Acad. Sci. 906, 39–43.
Wikman, F., Lu, M., Thykjaer, T., et al. (2000) Evaluation of the performance of a p53 sequencing microarray chip using 140 previously sequenced bladder tumor samples. Clin. Chem. 46(10), 1555–1561.
Beroud, C., Verdier, F., and Soussi, T. (1996) p53 gene mutation: software and database. Nucleic Acid Res. 24, 147–150.
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© 2004 Humana Press Inc., Totowa, NJ
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Wen, WH., Press, M.F. (2004). Identification of TP53 Mutations in Human Cancers Using Oligonucleotide Microarrays. In: Roulston, J.E., Bartlett, J.M.S. (eds) Molecular Diagnosis of Cancer. Methods in Molecular Medicine, vol 97. Humana Press. https://doi.org/10.1385/1-59259-760-2:323
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DOI: https://doi.org/10.1385/1-59259-760-2:323
Publisher Name: Humana Press
Print ISBN: 978-1-58829-160-8
Online ISBN: 978-1-59259-760-4
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