li fraumeni syndrome


Summary: Rare autosomal dominant syndrome characterized by mesenchymal and epithelial neoplasms at multiple sites. MUTATION of the p53 tumor suppressor gene, a component of the DNA DAMAGE response pathway, apparently predisposes family members who inherit it to develop certain cancers. The spectrum of cancers in the syndrome was shown to include, in addition to BREAST CANCER and soft tissue sarcomas (SARCOMA); BRAIN TUMORS; OSTEOSARCOMA; LEUKEMIA; and ADRENOCORTICAL CARCINOMA.

Top Publications

  1. Prochazkova K, Foretova L, Sedlacek Z. A rare tumor and an ethical dilemma in a family with a germline TP53 mutation. Cancer Genet Cytogenet. 2008;180:65-9 pubmed
    ..The case illustrates ethical problems associated with early predisposition testing in LFS, and the lack of consensus on this issue in the literature...
  2. Birch J, Alston R, McNally R, Evans D, Kelsey A, Harris M, et al. Relative frequency and morphology of cancers in carriers of germline TP53 mutations. Oncogene. 2001;20:4621-8 pubmed
    ..We conclude that germline TP53 mutations do not simply increase general cancer risk. There are tissue-specific effects...
  3. Frebourg T, Barbier N, Yan Y, Garber J, Dreyfus M, Fraumeni J, et al. Germ-line p53 mutations in 15 families with Li-Fraumeni syndrome. Am J Hum Genet. 1995;56:608-15 pubmed
    ..abstract truncated at 250 words)..
  4. Varley J, McGown G, Thorncroft M, Santibanez Koref M, Kelsey A, Tricker K, et al. Germ-line mutations of TP53 in Li-Fraumeni families: an extended study of 39 families. Cancer Res. 1997;57:3245-52 pubmed
    ..This could reflect our analysis of all 11 exons of TP53, including noncoding regions, as well as the use of direct sequencing rather than other less-sensitive mutation detection methods...
  5. Kuperwasser C, Hurlbut G, Kittrell F, Dickinson E, Laucirica R, Medina D, et al. Development of spontaneous mammary tumors in BALB/c p53 heterozygous mice. A model for Li-Fraumeni syndrome. Am J Pathol. 2000;157:2151-9 pubmed
    ..These results demonstrate the critical role that the p53 tumor suppressor gene plays in preventing tumorigenesis in the mammary gland...
  6. Lynch C, Milner J. Loss of one p53 allele results in four-fold reduction of p53 mRNA and protein: a basis for p53 haplo-insufficiency. Oncogene. 2006;25:3463-70 pubmed
    ..These observations identify a molecular basis for wild-type p53 haplo-insufficiency, which may explain the attenuated tumour-suppressive phenotype observed in cells with a single wild-type p53 allele and in humans with LFS...
  7. Petitjean A, Achatz M, Borresen Dale A, Hainaut P, Olivier M. TP53 mutations in human cancers: functional selection and impact on cancer prognosis and outcomes. Oncogene. 2007;26:2157-65 pubmed
    ..Further studies are needed to determine how TP53 haplotypes or loss of alleles interact with mutations to modulate their impact on cancer development and prognosis...
  8. Gonzalez K, Noltner K, Buzin C, Gu D, Wen Fong C, Nguyen V, et al. Beyond Li Fraumeni Syndrome: clinical characteristics of families with p53 germline mutations. J Clin Oncol. 2009;27:1250-6 pubmed publisher
    ..A clinical testing cohort was used to gain a broader understanding of the spectrum of tumors associated with germline p53 mutations to aid clinicians in identifying high-risk families...
  9. Birch J, Hartley A, Tricker K, Prosser J, Condie A, Kelsey A, et al. Prevalence and diversity of constitutional mutations in the p53 gene among 21 Li-Fraumeni families. Cancer Res. 1994;54:1298-304 pubmed
    ..These observations have important implications for asymptomatic carriers of germline p53 mutations, and there is a need for international collaboration in the development of protocols for the management of such families...

More Information

Publications106 found, 100 shown here

  1. Varley J. Germline TP53 mutations and Li-Fraumeni syndrome. Hum Mutat. 2003;21:313-20 pubmed
  2. Trahair T, Andrews L, Cohn R. Recognition of Li Fraumeni syndrome at diagnosis of a locally advanced extremity rhabdomyosarcoma. Pediatr Blood Cancer. 2007;48:345-8 pubmed
    ..cancer in a mother and an extremity rhabdomyosarcoma (RMS) in her daughter led to the diagnosis of the Li Fraumeni syndrome (LFS)...
  3. Bougeard G, Sesboue R, Baert Desurmont S, Vasseur S, Martin C, Tinat J, et al. Molecular basis of the Li-Fraumeni syndrome: an update from the French LFS families. J Med Genet. 2008;45:535-8 pubmed publisher
  4. Evans D, Lunt P, Clancy T, Eeles R. Childhood predictive genetic testing for Li-Fraumeni syndrome. Fam Cancer. 2010;9:65-9 pubmed publisher
    ..However, as yet no evidence based surveillance programme has been identified. We describe our experience of childhood testing for four children in two Li-Fraumeni families caused by TP53 mutations. ..
  5. Altaha R, Reed E, Abraham J. Breast and ovarian cancer genetics and prevention. W V Med J. 2003;99:187-91 pubmed
    ..Likewise, genetic counseling prior to testing is important, considering the major impact of the test results on an individual's life...
  6. Brugieres L. [Genetic predisposition to cancer in children]. Rev Prat. 2007;57:1065-7 pubmed
  7. Marcel V, Palmero E, Falagan Lotsch P, Martel Planche G, Ashton Prolla P, Olivier M, et al. TP53 PIN3 and MDM2 SNP309 polymorphisms as genetic modifiers in the Li-Fraumeni syndrome: impact on age at first diagnosis. J Med Genet. 2009;46:766-72 pubmed publisher
  8. Vornanen M, Aktan Collan K, Hallowell N, Konttinen H, Kaariainen H, Haukkala A. "I would like to discuss it further with an expert": a focus group study of Finnish adults' perspectives on genetic secondary findings. J Community Genet. 2018;9:305-314 pubmed publisher
    ..Discussion around SFs needs to concern not only which findings to report, but also how healthcare systems need to prepare for providing timely access to preventive care and support for individuals and families. ..
  9. Nasr A, Nutini M, Palombo B, Guerra E, Alberti S. Mutations of TP53 induce loss of DNA methylation and amplification of the TROP1 gene. Oncogene. 2003;22:1668-77 pubmed
    ..Taken together, these findings demonstrate that the inactivation of TP53 induces loss of DNA methylation and DNA methylation-dependent gene amplification. ..
  10. Nevanlinna H, Bartek J. The CHEK2 gene and inherited breast cancer susceptibility. Oncogene. 2006;25:5912-9 pubmed
    ..Finally, the potential value of information about the CHEK2 status in family counseling and optimizition of individualized cancer treatment is discussed. ..
  11. Chompret A. The Li-Fraumeni syndrome. Biochimie. 2002;84:75-82 pubmed
    ..The identification of germline p53 mutations in rare cancer-prone families has given rise to the medical, counseling, psychological and ethical problems. ..
  12. Soussi T, Beroud C. Assessing TP53 status in human tumours to evaluate clinical outcome. Nat Rev Cancer. 2001;1:233-40 pubmed
    ..What simple steps can be taken to ensure that patients benefit from our understanding of TP53? ..
  13. Peterson S, Pentz R, Marani S, Ward P, Blanco A, LaRue D, et al. Psychological functioning in persons considering genetic counseling and testing for Li-Fraumeni syndrome. Psychooncology. 2008;17:783-9 pubmed publisher
    ..Individual perceptions about cancer risk and p53 genetic testing, as well as personal experience with FDRs' cancer diagnoses and deaths, should be addressed during the counseling and testing process for LFS-affected families. ..
  14. Xue Y, Raharja A, Sim W, Wong E, Rahmat S, Lane D. The hot-spot p53R172H mutant promotes formation of giant spermatogonia triggered by DNA damage. Oncogene. 2017;36:2002-2013 pubmed publisher
    ..The formation of GSG does not translate to higher efficacy of testicular tumorigenesis arising from mutant p53 cells, which might be due to the presence of delayed-onset of p53-independent apoptosis. ..
  15. Varley J, Attwooll C, White G, McGown G, Thorncroft M, Kelsey A, et al. Characterization of germline TP53 splicing mutations and their genetic and functional analysis. Oncogene. 2001;20:2647-54 pubmed
    ..Furthermore we have identified the usage of a non-consensus splice donor site in four families with an intron 4 splice donor mutation. ..
  16. Olivier M, Eeles R, Hollstein M, Khan M, Harris C, Hainaut P. The IARC TP53 database: new online mutation analysis and recommendations to users. Hum Mutat. 2002;19:607-14 pubmed
    ..In addition, a new on-line application to retrieve somatic mutation data and analyze mutation patterns is now available. We also discuss limitations on the use of the database and provide recommendations to users. ..
  17. Guran S, Beyan C, Nevruz O, Yakicier C, Tunca Y. A chronic myeloid leukemia-like syndrome case with del (12) (p12) in a Li-Fraumeni syndrome family. Clin Lab Haematol. 2005;27:135-8 pubmed
    ..The deletion in chromosome 12p12 with hereditary p53 mutation should have a critical role in chronic myeloid leukemia-like syndrome etiology in our case. ..
  18. Frebourg T, Kassel J, Lam K, Gryka M, Barbier N, Andersen T, et al. Germ-line 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;89:6413-7 pubmed
    ..The observation of a functionally silent germ-line mutation indicates that, before associating a germ-line tumor suppressor gene mutation with cancer risk, it is prudent to consider its functional significance. ..
  19. Schaefer K, Wai D, Poremba C, Diallo R, Boecker W, Dockhorn Dworniczak B. Analysis of TP53 germline mutations in pediatric tumor patients using DNA microarray-based sequencing technology. Med Pediatr Oncol. 2002;38:247-53 pubmed
  20. Tsutsui T, Kumakura S, Tamura Y, Tsutsui T, Sekiguchi M, Higuchi T, et al. Immortal, telomerase-negative cell lines derived from a Li-Fraumeni syndrome patient exhibit telomere length variability and chromosomal and minisatellite instabilities. Carcinogenesis. 2003;24:953-65 pubmed
  21. Szabó D, Zsippai A, Bendes M, Tömböl Z, Szabó P, Racz K, et al. [Pathogenesis of adrenocortical cancer]. Orv Hetil. 2010;151:1163-70 pubmed publisher
    ..In this study, the pathogenesis of hereditary tumor syndromes, the alterations in sporadic tumors and the most recent molecular-bioinformatical observations are discussed. ..
  22. Villani A, Tabori U, Schiffman J, Shlien A, Beyene J, Druker H, et al. Biochemical and imaging surveillance in germline TP53 mutation carriers with Li-Fraumeni syndrome: a prospective observational study. Lancet Oncol. 2011;12:559-67 pubmed publisher
    ..Canadian Cancer Society Research Institute, Canadian Institutes of Health Research, SickKids Foundation, and Soccer for Hope. ..
  23. Hartley A, Blair V, Harris M, Birch J, Banerjee S, Freemont A, et al. Multiple primary tumours in a population-based series of patients with histopathologically peer-reviewed sarcomas. Br J Cancer. 1993;68:1243-6 pubmed
  24. Wallraven G, Nemunaitis J, Maples P. Compassionate approval process for experimental gene-based products. J Clin Oncol. 2008;26:1899-900 pubmed publisher
  25. Llovet P, Illana F, Martín Morales L, de la Hoya M, Garre P, Ibañez Royo M, et al. A novel TP53 germline inframe deletion identified in a Spanish series of Li-fraumeni syndrome suspected families. Fam Cancer. 2017;16:567-575 pubmed publisher
    ..The identification of novel TP53 alterations is crucial for a personalized cancer-risk management of the Li-Fraumeni syndrome. ..
  26. Pötzsch C, Voigtländer T, Lubbert M. p53 Germline mutation in a patient with Li-Fraumeni Syndrome and three metachronous malignancies. J Cancer Res Clin Oncol. 2002;128:456-60 pubmed
    ..The difficulties in the management and treatment of patients with this clinically heterogenous disorder are discussed. ..
  27. Ruijs M, Verhoef S, Rookus M, Pruntel R, van der Hout A, Hogervorst F, et al. TP53 germline mutation testing in 180 families suspected of Li-Fraumeni syndrome: mutation detection rate and relative frequency of cancers in different familial phenotypes. J Med Genet. 2010;47:421-8 pubmed publisher
    ..In addition to the risk for established LFS tumour types, TP53-positive individuals may also have an elevated risk for pancreatic and colon cancer. ..
  28. El Ghorayeb N, Grunenwald S, Nolet S, Primeau V, Cote S, Maugard C, et al. First case report of an adrenocortical carcinoma caused by a BRCA2 mutation. Medicine (Baltimore). 2016;95:e4756 pubmed publisher
    ..This is the first reported case of a patient with ACC associated with a BRCA2 germline mutation. Loss of heterozygosity in ACC DNA suggests a causal link with the BRCA2 8765delAG mutation. ..
  29. Ossa C, Molina G, Cock Rada A. Li-Fraumeni syndrome. Biomedica. 2016;36:182-7 pubmed publisher
    ..The diagnosis and management of Li-Fraumeni syndrome should be performed by a multidisciplinary team, and genetic counselling should be offered to patients and their relatives. ..
  30. Das K, Early D. Pancreatic Cancer Screening. Curr Treat Options Gastroenterol. 2017;15:562-575 pubmed publisher
  31. Rieske P, Zakrzewska M, Biernat W, Bartkowiak J, Zimmermann A, Liberski P. Atypical molecular background of glioblastoma and meningioma developed in a patient with Li-Fraumeni syndrome. J Neurooncol. 2005;71:27-30 pubmed
    ..Additionally, GB has a 1q LOH, which is an extremely rare alteration in glioblastomas. Identical 1q LOH was also observed in MFH. ..
  32. Ruijs M, Verhoef S, Wigbout G, Pruntel R, Floore A, de Jong D, et al. Late-onset common cancers in a kindred with an Arg213Gln TP53 germline mutation. Fam Cancer. 2006;5:169-74 pubmed
    ..Our findings suggest that this TP53 germline mutation is a causative factor in this family and that specific TP53 germline mutations can be associated with relatively late-onset common cancers. ..
  33. Tabori U, Nanda S, Druker H, Lees J, Malkin D. Younger age of cancer initiation is associated with shorter telomere length in Li-Fraumeni syndrome. Cancer Res. 2007;67:1415-8 pubmed
    ..Furthermore, telomere shortening could predict genetic anticipation observed in LFS and may serve as the first rational biological marker for clinical monitoring of these patients. ..
  34. O Neill A, Voss S, Jagannathan J, Kamihara J, Nibecker C, Itriago Araujo E, et al. Screening with whole-body magnetic resonance imaging in pediatric subjects with Li-Fraumeni syndrome: A single institution pilot study. Pediatr Blood Cancer. 2017;: pubmed publisher
    ..Whole-body magnetic resonance imaging (WB-MRI) may provide an acceptable method for early cancer detection...
  35. Felix C, Nau M, Takahashi T, Mitsudomi T, Chiba I, Poplack D, et al. Hereditary and acquired p53 gene mutations in childhood acute lymphoblastic leukemia. J Clin Invest. 1992;89:640-7 pubmed
    ..These data support the role of both hereditary and acquired p53 mutations in the pathogenesis and/or progression of some cases of childhood acute lymphoblastic leukemia. ..
  36. Abrahams P, Houweling A, Cornelissen Steijger P, Jaspers N, Darroudi F, Meijers C, et al. Impaired DNA repair capacity in skin fibroblasts from various hereditary cancer-prone syndromes. Mutat Res. 1998;407:189-201 pubmed
    ..These observations indicate that various hereditary cancer-prone syndromes, carrying mutations in different tumor-suppressor genes, exhibit an unexplained impairment of the capacity to repair UV-damaged DNA. ..
  37. Hill K, Wang J, Farwell K, Scaringe W, Sommer S. Spontaneous multiple mutations show both proximal spacing consistent with chronocoordinate events and alterations with p53-deficiency. Mutat Res. 2004;554:223-40 pubmed
    ..The enhancement of doublets in p53-deficient mice may contribute to cancer risk. ..
  38. Adeyanju M, Ilori A. Multiple primary tumors. Niger J Clin Pract. 2017;20:1346-1349 pubmed publisher
    ..It is necessary to make proper clinical and histopathological diagnosis and to institute proper management. We report the case of a woman who had primary cancers involving rare organ combinations of the breast and ascending colon...
  39. Bemis L, Robinson W, McFarlane R, Buyers E, Kelly K, Varella Garcia M, et al. EGFR-mutant lung adenocarcinoma in a patient with Li-Fraumeni syndrome. Lancet Oncol. 2007;8:559-60 pubmed
  40. Yamada H, Shinmura K, Okudela K, Goto M, Suzuki M, Kuriki K, et al. Identification and characterization of a novel germ line p53 mutation in familial gastric cancer in the Japanese population. Carcinogenesis. 2007;28:2013-8 pubmed
    ..These results suggest that Ile31-type p53 may be partly involved in FGC because of its low transcriptional activity and low cell proliferation suppressing activity. ..
  41. Stoltze U, Skytte A, Roed H, Hasle H, Ejlertsen B, Overeem Hansen T, et al. Clinical characteristics and registry-validated extended pedigrees of germline TP53 mutation carriers in Denmark. PLoS ONE. 2018;13:e0190050 pubmed publisher
    ..Following recent advances in surveillance options of LFS patients, lack of pre-symptomatic testing may lead to the mismanagement of some individuals. ..
  42. Liu P, Kraus E, Wu T, Strong L, Tainsky M. Analysis of genomic instability in Li-Fraumeni fibroblasts with germline p53 mutations. Oncogene. 1996;12:2267-78 pubmed
    ..Such an activity, which is likely to be due to the p53(mut), could result in the high rate of chromosomal instability and allelic loss of the wild-type p53 observed as these cells spontaneously immortalize. ..
  43. Evans D, Birch J, Ramsden R, Sharif S, Baser M. Malignant transformation and new primary tumours after therapeutic radiation for benign disease: substantial risks in certain tumour prone syndromes. J Med Genet. 2006;43:289-94 pubmed
    ..This review indicates that much more caution is warranted regarding the use of radiation treatment for benign tumours in childhood and in tumour prone conditions such as the neurofibromatoses. ..
  44. Mirzayans R, Severin D, Murray D. Relationship between DNA double-strand break rejoining and cell survival after exposure to ionizing radiation in human fibroblast strains with differing ATM/p53 status: implications for evaluation of clinical radiosensitivity. Int J Radiat Oncol Biol Phys. 2006;66:1498-505 pubmed
    ..However, it appears that using this parameter as a predictor of radiosensitivity without knowledge of the cells' p53 status could lead to incorrect conclusions. ..
  45. Agarwalla P, Dunn I, Turner C, Ligon K, Schneider K, Smith E. A novel TP53 germline mutation in a family with a history of multiple malignancies: case report and review of the literature. Pediatr Neurosurg. 2008;44:501-8 pubmed publisher
    ..These syndromes markedly influence both the patient and family members and may alter postoperative treatment regimens. ..
  46. Watanabe T, Vital A, Nobusawa S, Kleihues P, Ohgaki H. Selective acquisition of IDH1 R132C mutations in astrocytomas associated with Li-Fraumeni syndrome. Acta Neuropathol. 2009;117:653-6 pubmed publisher
    ..This remarkably selective occurrence of R132C mutations may reflect differences in the sequence of genetic events, with a preference for R132C mutations in astrocytes or precursor cells that already carry a germline TP53 mutation. ..
  47. Macedo G, Araujo Vieira I, Brandalize A, Giacomazzi J, Inez Palmero E, Volc S, et al. Rare germline variant (rs78378222) in the TP53 3' UTR: Evidence for a new mechanism of cancer predisposition in Li-Fraumeni syndrome. Cancer Genet. 2016;209:97-106 pubmed publisher
    ..To our knowledge, this is the first description of rs78378222[C] in LFS/LFL patients. Moreover, these findings suggest that rs78378222[C] lead to haploinsufficiency of p53, a new mechanism of carcinogenesis in LFS/LFL. ..
  48. Stein T, Crighton D, Boyle J, Varley J, White R. RNA polymerase III transcription can be derepressed by oncogenes or mutations that compromise p53 function in tumours and Li-Fraumeni syndrome. Oncogene. 2002;21:2961-70 pubmed
    ..Our data suggest that p53 status can have a profound effect upon pol III transcription and hence on the biosynthetic capacity of cells...
  49. Iwakuma T, Lozano G, Flores E. Li-Fraumeni syndrome: a p53 family affair. Cell Cycle. 2005;4:865-7 pubmed
    ..Interestingly, the p53 point mutant mice had a similar phenotype to p53 family compound mutant mice suggesting that there is an interplay between the p53 family members in tumorigenesis and Li-Fraumeni syndrome...
  50. Boyle J, Greaves M, Camplejohn R, Birch J, Roberts S, Varley J. Radiation-induced G1 arrest is not defective in fibroblasts from Li-Fraumeni families without TP53 mutations. Br J Cancer. 1999;79:1657-64 pubmed
    ..Exceptions to the previously reported inverse correlation between G1 arrest and clonogenic radiation resistance were observed, indicating that these phenotypes are not strictly interdependent...
  51. Boyle J, Spreadborough A, Greaves M, Birch J, Varley J, Scott D. Delayed chromosome changes in gamma-irradiated normal and Li-Fraumeni fibroblasts. Radiat Res. 2002;157:158-65 pubmed
    ..Our findings raise questions about the validity of quantitative extrapolation of cytogenetic data from Trp53-defective mice to radiogenic cancer risk in humans...
  52. Varley J. TP53, hChk2, and the Li-Fraumeni syndrome. Methods Mol Biol. 2003;222:117-29 pubmed
    ..It will be fascinating to see what genetic defects are responsible, and whether they involve additional components of DNA damage recognition, repair, or cell cycle checkpoint pathways...
  53. Kim I, Kang H, Shin Y, Yoo B, Yang H, Park J. Familial gastric cancers with Li-Fraumeni Syndrome: a case repast. World J Gastroenterol. 2005;11:4124-6 pubmed
  54. Bougeard G, Baert Desurmont S, Tournier I, Vasseur S, Martin C, Brugieres L, et al. Impact of the MDM2 SNP309 and p53 Arg72Pro polymorphism on age of tumour onset in Li-Fraumeni syndrome. J Med Genet. 2006;43:531-3 pubmed
    ..Polymorphisms affecting p53 degradation therefore represent one of the rare examples of modifier genetic factors identified to date in mendelian predispositions to cancer...
  55. Senzer N, Nemunaitis J, Nemunaitis M, Lamont J, Gore M, Gabra H, et al. p53 therapy in a patient with Li-Fraumeni syndrome. Mol Cancer Ther. 2007;6:1478-82 pubmed
    ..Relationships between these clinical, radiographic, and molecular markers may prove useful in guiding future application of p53 tumor suppressor therapy...
  56. Shlien A, Tabori U, Marshall C, Pienkowska M, Feuk L, Novokmet A, et al. Excessive genomic DNA copy number variation in the Li-Fraumeni cancer predisposition syndrome. Proc Natl Acad Sci U S A. 2008;105:11264-9 pubmed publisher
    ..Our results suggest that screening families predisposed to cancer for CNVs may identify individuals with an abnormally high number of these events...
  57. Lammens C, Bleiker E, Aaronson N, Vriends A, Ausems M, Jansweijer M, et al. Attitude towards pre-implantation genetic diagnosis for hereditary cancer. Fam Cancer. 2009;8:457-64 pubmed publisher
    ..The actual uptake, however, is expected to be lower. There is no indication that psychosocial factors affect interest in PGD...
  58. Ginsburg O, Akbari M, Aziz Z, Young R, Lynch H, Ghadirian P, et al. The prevalence of germ-line TP53 mutations in women diagnosed with breast cancer before age 30. Fam Cancer. 2009;8:563-7 pubmed publisher
    ..No TP53 mutation was found. This study does not support a policy that TP53 testing should be offered routinely to unselected women with early-onset breast cancer in the absence of a family history of cancer...
  59. Xian W, Miron A, Roh M, Semmel D, Yassin Y, Garber J, et al. The Li-Fraumeni syndrome (LFS): a model for the initiation of p53 signatures in the distal Fallopian tube. J Pathol. 2010;220:17-23 pubmed publisher
    ..This is in keeping with a general model of carcinogenesis, in which different and often independent risk factors operate at multiple points in the serous carcinogenic spectrum...
  60. Palmero E, Achatz M, Ashton Prolla P, Olivier M, Hainaut P. Tumor protein 53 mutations and inherited cancer: beyond Li-Fraumeni syndrome. Curr Opin Oncol. 2010;22:64-9 pubmed publisher
  61. Kruk P, Bohr V. Telomeric length in individuals and cell lines with altered p53 status. Radiat Oncol Investig. 1999;7:13-21 pubmed
    ..We also found that altered p53 expression in selected cancer cell model systems may be associated with shortened telomeric length, but did not appear to be associated with significant alterations in telomerase activity...
  62. Kimmelman A, Liang B. Familial neurogenic tumor syndromes. Hematol Oncol Clin North Am. 2001;15:1073-84 pubmed
    ..Study of these individuals and families has led to the discovery of genes that are an intrinsic aspect of cell regulation and will continue to be relevant in defining mechanisms of neoplastic development in brain and other tissues...
  63. Anensen N, Skavland J, Stapnes C, Ryningen A, Børresen Dale A, Gjertsen B, et al. Acute myelogenous leukemia in a patient with Li-Fraumeni syndrome treated with valproic acid, theophyllamine and all-trans retinoic acid: a case report. Leukemia. 2006;20:734-6 pubmed
  64. Ruijs M, Schmidt M, Nevanlinna H, Tommiska J, Aittomaki K, Pruntel R, et al. The single-nucleotide polymorphism 309 in the MDM2 gene contributes to the Li-Fraumeni syndrome and related phenotypes. Eur J Hum Genet. 2007;15:110-4 pubmed
    ..The higher prevalence of MDM2 SNP309 homozygous G/G carriers in the TP53-negative group suggests that this allele contributes to cancer susceptibility in LFS and LFS-related families...
  65. Agir H, MacKinnon C, Tan S. Li-Fraumeni syndrome: a case with 4 separate primary sarcomas and 5 sequential free flaps in the maxillofacial region. J Oral Maxillofac Surg. 2008;66:1714-9 pubmed publisher
  66. Reuss D, von Deimling A. Hereditary tumor syndromes and gliomas. Recent Results Cancer Res. 2009;171:83-102 pubmed publisher
    ..Therefore research on hereditary syndromes contributes substantially to our understanding of tumor formation...
  67. De Moura J, Kavalec F, Doghman M, Rosati R, Custodio G, Lalli E, et al. Heterozygous TP53stop146/R72P fibroblasts from a Li-Fraumeni syndrome patient with impaired response to DNA damage. Int J Oncol. 2010;36:983-90 pubmed
  68. Sedlacek Z, Kodet R, Kriz V, Seemanova E, Vodvarka P, Wilgenbus P, et al. Two Li-Fraumeni syndrome families with novel germline p53 mutations: loss of the wild-type p53 allele in only 50% of tumours. Br J Cancer. 1998;77:1034-9 pubmed
    ..These results support the view that complete loss of activity of the wild-type p53 need not be the initial event in the formation of all tumours in Li-Fraumeni individuals...
  69. Bell D, Varley J, Szydlo T, Kang D, Wahrer D, Shannon K, et al. Heterozygous germ line hCHK2 mutations in Li-Fraumeni syndrome. Science. 1999;286:2528-31 pubmed
  70. Herbert B, Wright A, Passons C, Wright W, Ali I, Kopelovich L, et al. Effects of chemopreventive and antitelomerase agents on the spontaneous immortalization of breast epithelial cells. J Natl Cancer Inst. 2001;93:39-45 pubmed
    ..We, therefore, tested whether immortalization of these cells could be prevented by treating them with chemopreventive agents and by inhibiting telomerase activity...
  71. Balmana J, Nomdedeu J, Diez O, Sabaté J, Balil A, Pericay C, et al. [Description of a new TP53 gene germline mutation in a family with the Li-Fraumeni syndrome. Genetic counselling to healthy mutation carriers]. Med Clin (Barc). 2002;119:497-9 pubmed
    ..Germline mutations in gene TP53 are identified in a percentage of affected families...
  72. Elmore L, Turner K, Gollahon L, Landon M, Jackson Cook C, Holt S. Telomerase protects cancer-prone human cells from chromosomal instability and spontaneous immortalization. Cancer Biol Ther. 2002;1:391-7 pubmed
    ..Using a model for Li Fraumeni Syndrome (LFS), infection of human telomerase resulted in maintenance of telomere lengths, extension of in vitro ..
  73. Scarpa A, Moore P. Genetics of gastric cancer: clinical implications. Suppl Tumori. 2003;2:S10-3 pubmed
  74. Kim I, Kang H, Shin Y, Park H, Jang S, Han S, et al. A TP53-truncating germline mutation (E287X) in a family with characteristics of both hereditary diffuse gastric cancer and Li-Fraumeni syndrome. J Hum Genet. 2004;49:591-5 pubmed
    ..Our results suggest that TP53 mutational screening in FGC families should be interpreted with caution because additional TP53 mutation-carrying HDGC families may also show LFS-related phenotypes...
  75. Peterson S, Pentz R, Blanco A, Ward P, Watts B, Marani S, et al. Evaluation of a decision aid for families considering p53 genetic counseling and testing. Genet Med. 2006;8:226-33 pubmed
    ..We evaluated outcomes following the administration of a video-based decision aid (DA) prior to clinical p53 genetic counseling and testing among persons who had previously participated in cancer genetics research...
  76. Tena Sanabria M, Herrera Sánchez D, Hernandez Lopez J, Huicochea Montiel J, Rodriguez A. [Li-Fraumeni familial cancer syndrome: case report and review of the literature]. Acta Ortop Mex. 2007;21:99-104 pubmed
    ..Multiple familial cancer is a rare entity as is also Li-Fraumeni Syndrome (LFS), which involves a mutation in the germ cell line of Tp53 suppresor gene that is expressed in chromosome 17p13.1 and occurs as an autosomal dominant condition...
  77. Dehner L, Hill D. Adrenal cortical neoplasms in children: why so many carcinomas and yet so many survivors?. Pediatr Dev Pathol. 2009;12:284-91 pubmed publisher
    ..A risk assessment system is proposed that incorporates tumor weight, localization of tumor to the gland without invasion into the surrounding tissues or organs, and absence of metastasis...
  78. Boyle J, Spreadborough A, Greaves M, Birch J, Varley J, Scott D. The relationship between radiation-induced G(1)arrest and chromosome aberrations in Li-Fraumeni fibroblasts with or without germline TP53 mutations. Br J Cancer. 2001;85:293-6 pubmed
    ..In LF cells with or without TP53 mutations, the reduced capacity to eliminate or repair chromosomal damage of the type induced by ionising radiation, may contribute to cancer predisposition in this syndrome...
  79. Lee S, Kim S, Bell D, Wahrer D, Schiripo T, Jorczak M, et al. Destabilization of CHK2 by a missense mutation associated with Li-Fraumeni Syndrome. Cancer Res. 2001;61:8062-7 pubmed
    b>Li Fraumeni Syndrome (LFS) is a multicancer phenotype, most commonly associated with germ-line mutations in TP53...
  80. Sodha N, Houlston R, Bullock S, Yuille M, Chu C, Turner G, et al. Increasing evidence that germline mutations in CHEK2 do not cause Li-Fraumeni syndrome. Hum Mutat. 2002;20:460-2 pubmed
  81. Olivier M, Goldgar D, Sodha N, Ohgaki H, Kleihues P, Hainaut P, et al. Li-Fraumeni and related syndromes: correlation between tumor type, family structure, and TP53 genotype. Cancer Res. 2003;63:6643-50 pubmed
    ..004). These observations have clinical implications for genetic testing and tumor surveillance in LFS/LFL families...
  82. Lang G, Iwakuma T, Suh Y, Liu G, Rao V, Parant J, et al. Gain of function of a p53 hot spot mutation in a mouse model of Li-Fraumeni syndrome. Cell. 2004;119:861-72 pubmed
    ..These results provide in vivo validation for the gain-of-function properties of certain p53 missense mutations and suggest a mechanistic basis for these phenotypes...
  83. Walsh T, Casadei S, Coats K, Swisher E, Stray S, Higgins J, et al. Spectrum of mutations in BRCA1, BRCA2, CHEK2, and TP53 in families at high risk of breast cancer. JAMA. 2006;295:1379-88 pubmed
    ..Furthermore, other breast cancer genes generally are not evaluated...
  84. Hill K, Buettner V, Heidt A, Chen L, Li W, Gonzalez K, et al. Most spontaneous tumors in a mouse model of Li-Fraumeni syndrome do not have a mutator phenotype. Carcinogenesis. 2006;27:1860-6 pubmed
    ..However, the data clearly show key differences in tumors from p53+/- mice compared with mismatch repair deficient tumors; a lack of dramatic increase in mutation frequency and absence of a signature of mutation...
  85. Sherif Z, Danielsen M. Balanced t(11;15)(q23;q15) in a TP53+/+ breast cancer patient from a Li-Fraumeni syndrome family. Cancer Genet Cytogenet. 2006;168:50-8 pubmed
    ..These data may implicate the region at breakpoint 11q23 and/or 15q15 as playing a significant role in predisposition to breast cancer development...
  86. Trkova M, Prochazkova K, Krutilkova V, Sumerauer D, Sedlacek Z. Telomere length in peripheral blood cells of germline TP53 mutation carriers is shorter than that of normal individuals of corresponding age. Cancer. 2007;110:694-702 pubmed
    ..In the current study a possible relation was analyzed between telomere length and cancer onset in TP53 mutation carriers...
  87. Iau P, Macmillan R, Blamey R. Germ line mutations associated with breast cancer susceptibility. Eur J Cancer. 2001;37:300-21 pubmed
    ..Most of the available data are derived from studies on highly selected populations. The importance of other less penetrant, but more prevalent, germ line mutations may be realised in the future...
  88. Varley J, McGown G, Thorncroft M, Kelsey A, Birch J. Significance of intron 6 sequence variations in the TP53 gene in Li-Fraumeni syndrome. Cancer Genet Cytogenet. 2001;129:85-7 pubmed
    ..We find no evidence for intron 6 sequence variants predisposing to LFS in our cohort of families and, furthermore, we show that some of the conclusions of other groups cannot be supported by data from our analysis...
  89. Evans S, Liang M, Amos C, Gu X, Lozano G. A novel genetic modifier of p53, mop1, results in embryonic lethality. Mamm Genome. 2004;15:415-23 pubmed
    ..Using simple-sequence length polymorphism analysis of the entire genome, we identified a putative chromosomal region for this modifier of p53 on mouse chromosome 11 centromeric to p53...
  90. Ayanga B, Price R, Gu X, Lozano G, Evans S. Genetic mapping of a putative tumor suppressor locus that influences tumorigenesis and metastasis in mice. Genes Chromosomes Cancer. 2006;45:668-75 pubmed
    ..Using simple-sequence length polymorphism analysis for loss of heterozygosity in tumors, we identified a putative tumor suppressor locus within 1 cM on mouse chromosome 11, which encompasses 12 mapped genes...
  91. Nemunaitis J, Nemunaitis J. Potential of Advexin: a p53 gene-replacement therapy in Li-Fraumeni syndrome. Future Oncol. 2008;4:759-68 pubmed publisher
    ..This review will summarize background knowledge of Li-Fraumeni syndrome, mechanisms of Advexin and clinical response of cancer to Advexin with a focus on Li-Fraumeni syndrome...
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