Inherited TP53 mutations are associated with a rare autosomal dominant disorder, the Li-Fraumeni syndrome (LFS). LFS is characterized by multiple primary neoplasms in children and young adults, with a predominance of soft-tissue sarcomas, osteosarcomas, breast cancers, brain tumors and adrenocortical carcinomas.

The dataset of germline mutations contains information on families in which at least one family member has been identied as a carrier of a germline mutation in the TP53 gene. Data are extracted from peer-reviewed articles. Unpublished data from Eeles et al. are also included. Criteria for inclusion are the following: a) individuals carrying a sequenced TP53 germline mutation, affected or not by a cancer, b) individuals affected by a cancer and belonging to a family in which at least one family member has been identied as a carrier of a germline mutation in the TP53 gene.

The R15 release includes 588 mutations described in 584 families or individuals. Information on individuals, pedigree and tumors is provided.

Statistics on previous releases are provided at the page: Database Statistics.

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To learn more on LFS and TP53 germline mutations, watch the videocast of the Li-Fraumeni Syndrome Workshop 2010.

See also OMIM,  GeneClinics, Cancer.gov and the following publications:

- Tabori U, Malkin D. Risk stratification in cancer predisposition syndromes: lessons learned from novel molecular developments in Li-Fraumeni syndrome. Cancer Res. 2008 Apr 1;68(7):2053-7. Review.

- Olivier M, Goldgar DE, Sodha N, Ohgaki H, Kleihues P, Hainaut P, Eeles RA. Li-Fraumeni and related syndromes: correlation between tumor type, family structure, and TP53 genotype. Cancer Res. 2003 Oct 15;63(20):6643-50.

- Varley JM. Germline TP53 mutations and Li-Fraumeni syndrome. Hum Mutat 2003 Mar;21(3):313-20.

- Birch JM, Alston RD, McNally RJ, Evans DG, Kelsey AM, Harris M, Eden OB, Varley JM. Relative frequency and morphology of cancers in carriers of germline TP53 mutations. Oncogene 2001 Aug 2;20(34):4621-8.

- Nichols KE, Malkin D, Garber JE, Fraumeni JF Jr, Li FP. Germ-line p53 mutations predispose to a wide spectrum of early-onset cancers. Cancer Epidemiol Biomarkers Prev. 2001 Feb;10(2):83-7.

- Birch JM, Blair V, Kelsey AM, Evans DG, Harris M, Tricker KJ, Varley JM. Cancer phenotype correlates with constitutional TP53 genotype in families with the Li-Fraumeni syndrome. Oncogene. 1998 Sep 3;17(9):1061-8.

- Varley JM, Evans DG, Birch JM. Li-Fraumeni syndrome--a molecular and clinical review. Br J Cancer. 1997;76(1):1-14.

Other interesting papers:

- Gonzalez KD, Noltner KA, Buzin CH, Gu D, Wen-Fong CY, Nguyen VQ, Han JH, Lowstuter K, Longmate J, Sommer SS, Weitzel JN. Beyond Li Fraumeni Syndrome: clinical characteristics of families with p53 germline mutations. J Clin Oncol. 2009 Mar 10;27(8):1250-6.

- Shlien A, Tabori U, Marshall CR, Pienkowska M, Feuk L, Novokmet A, Nanda S, Druker H, Scherer SW, Malkin D. Excessive genomic DNA copy number variation in the Li-Fraumeni cancer predisposition syndrome. Proc Natl Acad Sci U S A. 2008 Aug 12;105(32):11264-9.

- 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 Feb 15;67(4):1415-8.

- Achatz MI, Olivier M, Calvez FL, Martel-Planche G, Lopes A, Rossi BM, Ashton-Prolla P, Giugliani R, Palmero EI, Vargas FR, Rocha JC, Vettore AL, Hainaut P. The TP53 mutation, R337H, is associated with Li-Fraumeni and Li-Fraumeni-like syndromes in Brazilian families. Cancer Letters 2007 Jan 8;245(1-2):96-102.

- Bond GL, Hirshfield KM, Kirchhoff T, Alexe G, Bond EE, Robins H, Bartel F, Taubert H, Wuerl P, Hait W, Toppmeyer D, Offit K, Levine AJ. MDM2 SNP309 accelerates tumor formation in a gender-specific and hormone-dependent manner. Cancer Res. 2006 May 15;66(10):5104-10.

- Lalloo F, Varley J, Moran A, Ellis D, O'dair L, Pharoah P, Antoniou A, Hartley R, Shenton A, Seal S, Bulman B, Howell A, Evans DG. BRCA1, BRCA2 and TP53 mutations in very early-onset breast cancer with associated risks to relatives. Eur J Cancer. 2006 May;42(8):1143-50.

- Bougeard G, Baert-Desurmont S, Tournier I, Vasseur S, Martin C, Brugieres L, Chompret A, Bressac-de Paillerets B, Stoppa-Lyonnet D, Bonaiti-Pellie C, Frebourg T. Impact of the MDM2 SNP309 and p53 Arg72Pro polymorphism on age of tumour onset in Li-Fraumeni syndrome. J Med Genet. 2006 Jun;43(6):531-3.

- Wong P, Verselis SJ, Garber JE, Schneider K, DiGianni L, Stockwell DH, Li FP, Syngal S. Prevalence of early onset colorectal cancer in 397 patients with classic Li-Fraumeni syndrome. Gastroenterology. 2006 Jan;130(1):73-9.

- Bachinski LL, Olufemi SE, Zhou X, Wu CC, Yip L, Shete S, Lozano G, Amos CI, Strong LC, Krahe R. Genetic mapping of a third Li-Fraumeni syndrome predisposition locus to human chromosome 1q23. Cancer Res. 2005 May;42(8):1143-50.

- Bond GL, Hu W, Bond EE, Robins H, Lutzker SG, Arva NC, Bargonetti J, Bartel F, Taubert H, Wuerl P, Onel K, Yip L, Hwang SJ, Strong LC, Lozano G, Levine AJ. A single nucleotide polymorphism in the MDM2 promoter attenuates the p53 tumor suppressor pathway and accelerates tumor formation in humans. Cell 2004 Nov 24;119(5):591-602.