Advertisement

TP53 Mutation and Li-Fraumeni Syndrome

  • Sydney D. Finkelstein
  • Frank S. Lieberman
Chapter
  • 1.6k Downloads

Abstract

Preeminent among human tumor suppressor genes in functionality and importance is TP53, reflected by its well-recognized characterization as “guardian of the genome.”1, 2, 3, 4, 5 TP53 is perhaps the most intensively studied human-cancer-associated oncoprotein, in keeping with its protean effects on critical cellular pathways, including transcriptional control of gene expression, cell cycle proliferation, DNA repair, apoptosis, and cellular maturation and differentiation.6, 7, 8 Mutational damage to TP53 is the single most common cancer DNA alteration, having been observed in more than 50% of all human cancers.9 Detection of TP53 mutation is now performed for several clinical indications including assessment of tumor biological aggressiveness, discrimination of tumor recurrence versus de novo cancer formation, determination of tumor anaplasia, and as part of a search for germline inherited mutational change associated with heightened cancer susceptibility.10,11 The emerging diagnostic and prognostic role attributed to TP53 mutation detection justifies testing in selected patients as part of the clinical molecular pathology workup of human cancer.

Keywords

Germline Mutation TP53 Mutation Allelic Loss TP53 Protein Germline TP53 Mutation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Lane DL. Cancer. p53, guardian of the genome. Nature. 1992;358:15–16.PubMedCrossRefGoogle Scholar
  2. 2.
    Finlay CA, Hinds PW, Levine AJ. The p53 proto-oncogene can act as a suppressor of transformation. Cell. 1989;57:1083–1093.PubMedCrossRefGoogle Scholar
  3. 3.
    Kastan MB, Zhan Q, El-Deiry WS. A mammalian cell cycle checkpoint pathway utilizing p53 and GADD45 is defective in ataxia telangiectasia. Cell. 1992;71:587–597.PubMedCrossRefGoogle Scholar
  4. 4.
    Kastan MB, Onyekwere O, Sidransky D, Vogelstein B, Craig RW. Participation of p53 in the cellular response to DNA damage. Cancer Res. 1991;51:6304–6311.PubMedGoogle Scholar
  5. 5.
    El-Deiry WS, Tokino T, Velculescu VE. WAF1, a potential mediator of p53 tumor suppression. Cell. 1993;75:817–825.PubMedCrossRefGoogle Scholar
  6. 6.
    Diller L, Kassel J, Nelson CE. p53 functions as a cell cycle control protein in osteosarcomas. Mol Cell Biol. 1990;10:5772–5781.PubMedGoogle Scholar
  7. 7.
    Shaulsky G, Goldfinger N, Peled A, Rotter V. Involvement of wildtype p53 in pre-B cell differentiation in vitro. Proc Natl Acad Sci U S A. 1991;88:8982–8986.PubMedCrossRefGoogle Scholar
  8. 8.
    Tarunina M, Jenkins JR. Human p53 binds DNA as a protein homodimer but monomeric variants retain full transcription transactivation activity. Oncogene. 1993;8:3165–3173.PubMedGoogle Scholar
  9. 9.
    Hollstein M, Sidransky D, Vogelstein B, Harris CC. p53 mutations in human cancers. Science. 1991;253:49–53.PubMedCrossRefGoogle Scholar
  10. 10.
    Finkelstein SD, Przygodzki RM, Pricolo VE, etc. Prediction of biological aggressiveness in colorectal cancer by p53/K-ras-2 topographic genotyping. Mol Diagn. 1996;1:5–28.PubMedCrossRefGoogle Scholar
  11. 11.
    Pollack IF, Hamilton RL, Finkelstein SD, et al. The relationship between mutations and overexpression of p53 and prognosis in malignant gliomas of childhood. Cancer Res. 1997;57:304–309.PubMedGoogle Scholar
  12. 12.
    Malkin D, Li FP, Strong LC. Germline p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms. Science. 1990;250:1233–1238.PubMedCrossRefGoogle Scholar
  13. 13.
    Frebourg T, Friend SH. Cancer risks from germline p53 mutations. J Clin Invest. 1992;90:1637–1641.PubMedCrossRefGoogle Scholar
  14. 14.
    Frebourg T, Kassel J, Lam KT. Germline mutations of the p53 tumor suppressor gene in patients with high risk for cancer inactivate the p53 protein. Proc Natl Acad Sci U S A. 1992;89:6413–6417.PubMedCrossRefGoogle Scholar
  15. 15.
    Varley JM, Evans DGR, Birch JM. Li-Fraumeni syndrome—a molecular and clinical review. Br J Cancer. 1997;1;1–14.Google Scholar
  16. 16.
    Lamb P, Crawford L. Characterization of the human p53 gene. Mol Cell Biol. 1986;6:1379–1385.PubMedGoogle Scholar
  17. 17.
    Pavletich NP, Chambers KA, Pabo CO. The DNA-binding domain of p53 contains the four conserved regions and the major mutation hot spots. Genes Dev. 1993;7:2556–2564.PubMedCrossRefGoogle Scholar
  18. 18.
    Reisman D, Greenberg M, Rotter V. Human p53 oncogene contains one promoter upstream of exon 1 and a second stronger promoter within intron 1. Proc Natl Acad Sci U S A. 1988;85:5146–5150.PubMedCrossRefGoogle Scholar
  19. 19.
    Holmquist GP, Gao S. Somatic mutation theory, DNA repair rates, and the molecular epidemiology of p53 mutations. Mutat Res. 1997;386:69–101.PubMedCrossRefGoogle Scholar
  20. 20.
    Fields S, Jang SK. Presence of a potent transcription activating sequence in the p53 protein. Science. 1990;249:1046–1049.PubMedCrossRefGoogle Scholar
  21. 21.
    Oren M, Prives C. p53: upstream, down-stream, and off stream. Review of the 8th p53 workshop. Biochim Biophys Acta. 1996;1288:R13–R19.PubMedGoogle Scholar
  22. 22.
    Momand J, Zambetti GP, Olson D, George D, Levine AJ. The mdm-2 oncogene product forms a complex with the p53 protein and inhibits p53-mediated transactivation. Cell. 1992;69:1237–1245.PubMedCrossRefGoogle Scholar
  23. 23.
    Oltvai ZN, Milliman CL, korsmeyer SJ. Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell. 1993;74:609–619.PubMedCrossRefGoogle Scholar
  24. 24.
    Bienz-Tadmor B, Zakut-Houri R, Libresco S, Givol D, Oren M. The 5′ region of the p53 gene: Evolutionary conservation and evidence for a negative regulatory element. EMBO J. 1985;4:3209–3213.PubMedGoogle Scholar
  25. 25.
    Hussain SP, Harris CC. Molecular epidemiology and carcinogenesis: endogenous and exogenous carcinogens. Mut Res. 2000;462:311–322.Google Scholar
  26. 26.
    DiGiammarino EL, Lee AS, Cadwell C, et al. A novel mechanism of tumorigenesis involving pH-dependent destabilization of a mutant p53 tetramer. Nat Struct Biol. 2002;9:12–16.PubMedCrossRefGoogle Scholar
  27. 27.
    Beroud C, Soucci T. p53 gene mutation: software and database. Nucleic Acids Res. 1998;26:200–204.PubMedCrossRefGoogle Scholar
  28. 28.
    Olivier M, Eeles R, Hollstein M, Khan MA, Harris CC, Hainaut P. The IARC TP53 database: new online mutation analysis and recommendations to users. Hum Mutat. 2002;19:607–614.PubMedCrossRefGoogle Scholar
  29. 29.
    Knudson AG. Mutation and cancer: statistical study of retinoblastoma. Proc Natl Acad Sci U S A. 1971;68:820–823.PubMedCrossRefGoogle Scholar
  30. 30.
    Knudson AG. Genetics and etiology of human cancer. Adv Hum Genet. 1977, 8:1–66.PubMedGoogle Scholar
  31. 31.
    Knudson AG. Hereditary cancer: two hits revisited. J Cancer Res Oncol. 1996;122:135–140.CrossRefGoogle Scholar
  32. 32.
    Li FP, Fraumeni F Jr. Soft-tissue sarcomas, breast cancer, and other neoplasms. a familial syndrome? Ann Intern Med. 1969;71:747–752.PubMedGoogle Scholar
  33. 33.
    Malkin D, Li FP, Fraumeni JF Jr. Germ-line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms. Science. 1990;250:1233–1238.PubMedCrossRefGoogle Scholar
  34. 34.
    Eng C, Hampel H, de la Chapelle A. Genetic testing for cancer predisposition. Annu Rev Med. 2001;52:371–400.PubMedCrossRefGoogle Scholar
  35. 35.
    Eng C, Schneider K, Fraumeni JF, Li FP. Third international workshop on collaborative interdisciplinary studies of p53 and other predisposing genes in Li-Fraumeni syndrome. Cancer Epidemiol Biomarkers Prev. 1997;6:379–383.PubMedGoogle Scholar
  36. 36.
    Toguchida J, Yamaguchi T, Dayton SH. Prevalence and spectrum of germline mutations of the p53 among patients with sarcomas. N Engl J Med. 1992;326:1301–1308.PubMedCrossRefGoogle Scholar
  37. 37.
    Birch JM, Hartley AL, Tricker KJ. Prevalence and diversity of constitutional mutations in the p53 gene among 21 Li-Fraumeni families. Cancer Res. 1994,54:1298–1304.PubMedGoogle Scholar
  38. 38.
    Varley JM, McGown G, Thorncroft M. Germ-line mutations of TP53 in Li-Fraumeni families: an extended study of 39 families. Cancer Res. 1997;57:3245–3252.PubMedGoogle Scholar
  39. 39.
    Baker SJ, Fearon ER, Nigro JM. Chromosomal 17 deletions and p53 mutations in colorectal carcinomas. Science. 1989;244:217–221.PubMedCrossRefGoogle Scholar
  40. 40.
    Righetti SC, Della Torre G, Pilotti S. A comparative study of p53 gene mutations, protein accumulation, and response to cisplatin-based chemotherapy in advanced ovarian carcinoma. Cancer Res. 1966;56:689–693.Google Scholar
  41. 41.
    Kovach JS, Hartmann A, Blaszyk H, Cunningham J, Schaid D, Sommer SS. Mutation detection by highly sensitive methods indicates that p53 gene mutations in breast cancer can have important prognostic value. Proc Natl Acad Sci U S A. 1996;93:1093–1096.PubMedCrossRefGoogle Scholar
  42. 42.
    Pricolo VE, Finkelstein SD, Hansen K, Cole BF, Bland KI. Mutated p53 gene is an independent adverse predictor of survival in colon carcinoma. Arch Surg. 1997;132:371–374.PubMedGoogle Scholar
  43. 43.
    Chozick BS, Weicker ME, Jackson CL, et al. Pattern of mutant P53 expression in human astrocytomas suggests the existence of alternative pathways of tumorigenesis. Cancer. 1994;73:406–415.PubMedCrossRefGoogle Scholar
  44. 44.
    Mashiyama S, Murakami Y, Yoshimoto T, Sekiya T, Hayashi K. Detection of p53 gene mutations in human brain tumors by single strand conformation polymorphism analysis of polymerase chain reaction products. Oncogene. 1991;6:1313–1318.PubMedGoogle Scholar
  45. 45.
    Pollack IF, Finkelstein SD, Burnham J, et al. Age and TP53 mutation frequency in childhood malignant gliomas: results in a multiinstitutional cohort. Cancer Res. 2001;61:7404–7407.PubMedGoogle Scholar
  46. 46.
    Takahashi T, Nan MM, Chiba I, Buchhagen DL, Mima JD. p53: a frequent target for genetic abnormalities in lung cancer. Science. 1989;246:491–494.PubMedCrossRefGoogle Scholar
  47. 47.
    Harris CC. The p53 tumor suppressor gene: at the crossroads of molecular carcinogenesis, molecular epidemiology, and cancer risk assessment. Science. 1993;262:1980–1981.PubMedCrossRefGoogle Scholar
  48. 48.
    Carbone DP, misudomi T, Chiba I. p53 immunostaining positivity is associated with reduced survival and is imperfectly correlated with gene mutations in resected non-small cell lung cancer. a preliminary report of LCSG 871. Chest. 1994;106(suppl):377S–381S.PubMedCrossRefGoogle Scholar
  49. 49.
    Eeles RA. Predictive testing for germline mutations in the p53 gene: are all the questions answered? Eur J Cancer. 1993;29A:1361–1315.PubMedCrossRefGoogle Scholar
  50. 50.
    Jolly KW, Malkin D, Douglass EC, Brown TF, Sinclair AE, Look AT. Splice-specific mutation of the p53 gene in a family with hereditary breast cancer. Oncogene. 1994;9:97–102.PubMedGoogle Scholar
  51. 51.
    Felix CA, Strauss EA, D’Amico D, et al. A novel germline p53 splicing mutation in a pediatric patient with a second malignant neoplasm. Oncogene. 1993;8:1203–1210.PubMedGoogle Scholar
  52. 52.
    Dreesen JC, Bras M, Coonen E, Dumoulin JC, Evers JL, Geraedts JP. Allelic dropout caused by allele-specific amplification failure in single-cell PCR of the cystic fibrosis delta F508 deletion. J Assist Reprod Genet. 1996;13:112–114.PubMedCrossRefGoogle Scholar
  53. 53.
    Finkelstein SD, Przygodzki R, Swalsky PA. Microdissection-based p53 genotyping: concepts for molecular testing. Mol Diagn. 1998;3:179–191.PubMedCrossRefGoogle Scholar
  54. 54.
    Wikman FP, Lu ML, Thykjaer T, et al. Evaluation of the performance of a p53 sequencing microarray chip using 140 previously sequenced bladder tumor samples. Clin Chem. 2000;46:1555–1561.PubMedGoogle Scholar
  55. 55.
    Safatle-Ribeiro AV, Ribeiro U Jr, Sakai P, et al. Integrated p53 histopathologic/genetic analysis of premalignant lesions of the esophagus. Cancer Detect Prev. 2000;24:13–23.PubMedGoogle Scholar
  56. 56.
    Hahn M, Fislage R, Pingoud A. Polymorphism of the pentanucleotide repeat d(AAAAT) within intron 1 of the human tumor suppressor gene p53 (17p13.1). Hum Genet. 1995;95:471–472.PubMedCrossRefGoogle Scholar
  57. 57.
    Kanbour-Shakir A, Kounelis S, Papadaki H, et al. Relationship of p53 genotype to second look recurrence and survival in ovarian epithelial malignancy. Mol Diagn. 1996;1:121–129.PubMedCrossRefGoogle Scholar
  58. 58.
    Ribiero U, Safatle-Ribiero A, Posner MC. Comparative P53 mutational analysis of multiple primary cancers of the upper aerodigestive tract. Surgery. 1996;120:45–53.CrossRefGoogle Scholar
  59. 59.
    Rolston R, Sasatomi S, Hunt J, Swalsky P, Finkelstein SD. Distinguishing de novo second cancer formation from tumor recurrence: mutational fingerprinting by microdissection genotyping. J Mol Diagn. 2001;3:129–132.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Sydney D. Finkelstein
    • 1
  • Frank S. Lieberman
    • 2
  1. 1.Redpath Integrated PathologyPittsburghUSA
  2. 2.Department of NeurologyUniversity of PittsburghPittsburghUSA

Personalised recommendations