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Li-Fraumeni syndrome 1(LFS1)

MedGen UID:
322656
Concept ID:
C1835398
Disease or Syndrome
Synonyms: LFS1; Li Fraumeni syndrome; Sarcoma family syndrome of Li and Fraumeni
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Autosomal dominant inheritance refers to genetic conditions that occur when a mutation is present in one copy of a given gene (i.e., the person is heterozygous).
 
Gene: TP53
Cytogenetic location: 17p13.1
OMIM: 151623

Disease characteristics

Excerpted from the GeneReview: Li-Fraumeni Syndrome
Li-Fraumeni syndrome (LFS) is a cancer predisposition syndrome associated with the development of the following classic tumors: soft tissue sarcoma, osteosarcoma, pre-menopausal breast cancer, brain tumors, adrenocortical carcinoma (ACC), and leukemias. In addition, a variety of other neoplasms may occur. LFS-related cancers often occur in childhood or young adulthood and survivors have an increased risk for multiple primary cancers. Age-specific cancer risks have been calculated.  [from GeneReviews]
Full text of GeneReview (by section):
Summary  |  Diagnosis  |  Clinical Description  |  Differential Diagnosis  |  Management  |  Genetic Counseling  |  Resources  |  Molecular Genetics  |  References  |  Chapter Notes
Authors:
Katherine Schneider  |  Kristin Zelley  |  Kim E Nichols, et. al.   view full author information

Additional descriptions

From OMIM
Li-Fraumeni syndrome (LFS) is a clinically and genetically heterogeneous inherited cancer syndrome. LFS is characterized by autosomal dominant inheritance and early onset of tumors, multiple tumors within an individual, and multiple affected family members. In contrast to other inherited cancer syndromes, which are predominantly characterized by site-specific cancers, LFS presents with a variety of tumor types. The most common types are soft tissue sarcomas and osteosarcomas, breast cancer, brain tumors, leukemia, and adrenocortical carcinoma. Classic LFS is defined as a proband with a sarcoma before the age of 45 years and a first-degree relative with any cancer before the age of 45 years and 1 additional first- or second-degree relative in the same lineage with any cancer before the age of 45 years or a sarcoma at any age (Li et al., 1988). Li-Fraumeni-like syndrome (LFL) is defined as a proband with any childhood cancer, or a sarcoma, brain tumor, or adrenocortical tumor before the age of 45 years, plus a first- or second-degree relative in the same lineage with a typical LFS tumor at any age, and an additional first- or second-degree relative in the same lineage with any cancer before the age of 60 years (Birch et al., 1994). A less restrictive definition of LFL is 2 different LFS-related tumors in first- or second-degree relatives at any age (Eeles, 1995). Approximately 70% of LFS cases and 40% of LFL cases contain germline mutations in the p53 gene on chromosome 17p13.1 (Bachinski et al., 2005). Genetic Heterogeneity of Li-Fraumeni Syndrome A second form of Li-Fraumeni syndrome (LFS2; 609265) is caused by mutation in the CHEK2 gene (604373), and an LFS locus (LFS3; 609266) has been mapped to chromosome 1q23.  http://www.omim.org/entry/151623
From GHR
Li-Fraumeni syndrome is a rare disorder that greatly increases the risk of developing several types of cancer, particularly in children and young adults. The cancers most often associated with Li-Fraumeni syndrome include breast cancer, a form of bone cancer called osteosarcoma, and cancers of soft tissues (such as muscle) called soft tissue sarcomas. Other cancers commonly seen in this syndrome include brain tumors, cancers of blood-forming tissues (leukemias), and a cancer called adrenocortical carcinoma that affects the outer layer of the adrenal glands (small hormone-producing glands on top of each kidney). Several other types of cancer also occur more frequently in people with Li-Fraumeni syndrome. A very similar condition called Li-Fraumeni-like syndrome shares many of the features of classic Li-Fraumeni syndrome. Both conditions significantly increase the chances of developing multiple cancers beginning in childhood; however, the pattern of specific cancers seen in affected family members is different.  http://ghr.nlm.nih.gov/condition/li-fraumeni-syndrome

Clinical features

Nephroblastoma (Wilms tumor)
MedGen UID:
505324
Concept ID:
CN002424
Finding
The presence of a `nephroblastoma` (MPATH:261), which is a neoplasm of the `kidney` (FMA:7203) that primarily affects children.
Osteosarcoma
MedGen UID:
505326
Concept ID:
CN002426
Finding
A malignant bone tumor that usually develops during adolescence and usually affects the long bones including the tibia, femur, and humerus. The typical symptoms of osteosarcoma comprise bone pain, fracture, limitation of motion, and tenderness or swelling at the site of the tumor.
Neoplasm of the pancreas
MedGen UID:
425115
Concept ID:
CN002617
Finding
The presence of a `neoplasm` (MPATH:218) of the `pancreas` (FMA:7198).
Breast carcinoma
MedGen UID:
428324
Concept ID:
CN002714
Finding
The presence of a `carcinoma` (MPATH:549) of the `breast` (FMA:9601).
Adrenocortical carcinoma
MedGen UID:
505968
Concept ID:
CN005871
Finding
A malignant neoplasm of the adrenal cortex that may produce hormones such as cortisol, aldosterone, estrogen, or testosterone.
Nephroblastoma (Wilms tumor)
MedGen UID:
505324
Concept ID:
CN002424
Finding
The presence of a `nephroblastoma` (MPATH:261), which is a neoplasm of the `kidney` (FMA:7203) that primarily affects children.
Prostate cancer
MedGen UID:
506673
Concept ID:
CN167851
Finding
A cancer of the `prostate` (FMA:9600).
Breast carcinoma
MedGen UID:
428324
Concept ID:
CN002714
Finding
The presence of a `carcinoma` (MPATH:549) of the `breast` (FMA:9601).
Adrenocortical carcinoma
MedGen UID:
505968
Concept ID:
CN005871
Finding
A malignant neoplasm of the adrenal cortex that may produce hormones such as cortisol, aldosterone, estrogen, or testosterone.
Osteosarcoma
MedGen UID:
505326
Concept ID:
CN002426
Finding
A malignant bone tumor that usually develops during adolescence and usually affects the long bones including the tibia, femur, and humerus. The typical symptoms of osteosarcoma comprise bone pain, fracture, limitation of motion, and tenderness or swelling at the site of the tumor.
Neoplasm of the pancreas
MedGen UID:
425115
Concept ID:
CN002617
Finding
The presence of a `neoplasm` (MPATH:218) of the `pancreas` (FMA:7198).

Professional guidelines

PubMed

Green RC, Berg JS, Grody WW, Kalia SS, Korf BR, Martin CL, McGuire AL, Nussbaum RL, O'Daniel JM, Ormond KE, Rehm HL, Watson MS, Williams MS, Biesecker LG; American College of Medical Genetics and Genomics
Genet Med 2013 Jul;15(7):565-74. Epub 2013 Jun 20 doi: 10.1038/gim.2013.73. [Epub ahead of print] PMID: 23788249Free PMC Article
Robson ME, Storm CD, Weitzel J, Wollins DS, Offit K; American Society of Clinical Oncology
J Clin Oncol 2010 Feb 10;28(5):893-901. Epub 2010 Jan 11 doi: 10.1200/JCO.2009.27.0660. [Epub ahead of print] PMID: 20065170
Zon RT, Goss E, Vogel VG, Chlebowski RT, Jatoi I, Robson ME, Wollins DS, Garber JE, Brown P, Kramer BS; American Society of Clinical Oncology
J Clin Oncol 2009 Feb 20;27(6):986-93. Epub 2008 Dec 15 doi: 10.1200/JCO.2008.16.3691. [Epub ahead of print] PMID: 19075281Free PMC Article
Saslow D, Boetes C, Burke W, Harms S, Leach MO, Lehman CD, Morris E, Pisano E, Schnall M, Sener S, Smith RA, Warner E, Yaffe M, Andrews KS, Russell CA; American Cancer Society Breast Cancer Advisory Group
CA Cancer J Clin 2007 Mar-Apr;57(2):75-89. PMID: 17392385
Trepanier A, Ahrens M, McKinnon W, Peters J, Stopfer J, Grumet SC, Manley S, Culver JO, Acton R, Larsen-Haidle J, Correia LA, Bennett R, Pettersen B, Ferlita TD, Costalas JW, Hunt K, Donlon S, Skrzynia C, Farrell C, Callif-Daley F, Vockley CW; National Society of Genetic Counselors
J Genet Couns 2004 Apr;13(2):83-114. doi: 10.1023/B:JOGC.0000018821.48330.77. PMID: 15604628
American Society of Clinical Oncology
J Clin Oncol 2003 Jun 15;21(12):2397-406. Epub 2003 Apr 11 doi: 10.1200/JCO.2003.03.189. [Epub ahead of print] PMID: 12692171
Am J Hum Genet 1995 Nov;57(5):1233-41. PMID: 7485175Free PMC Article

Recent clinical studies

Etiology

Giacomazzi J, Selistre SG, Rossi C, Alemar B, Santos-Silva P, Pereira FS, Netto CB, Cossio SL, Roth DE, Brunetto AL, Zagonel-Oliveira M, Martel-Planche G, Goldim JR, Hainaut P, Camey SA, Ashton-Prolla P
Cancer 2013 Dec 15;119(24):4341-9. Epub 2013 Oct 7 doi: 10.1002/cncr.28346. [Epub ahead of print] PMID: 24122735
Chadaz T, Hobbs SK, Son H
Clin Nucl Med 2013 Oct;38(10):818-20. doi: 10.1097/RLU.0b013e3182a20033. PMID: 24107814
Magnusson S, Gisselsson D, Wiebe T, Kristoffersson U, Borg Å, Olsson H
Pediatr Blood Cancer 2012 Nov;59(5):846-53. Epub 2012 May 31 doi: 10.1002/pbc.24223. [Epub ahead of print] PMID: 22653678
Villani A, Tabori U, Schiffman J, Shlien A, Beyene J, Druker H, Novokmet A, Finlay J, Malkin D
Lancet Oncol 2011 Jun;12(6):559-67. Epub 2011 May 19 doi: 10.1016/S1470-2045(11)70119-X. [Epub ahead of print] PMID: 21601526
Masciari S, Dewanwala A, Stoffel EM, Lauwers GY, Zheng H, Achatz MI, Riegert-Johnson D, Foretova L, Silva EM, Digianni L, Verselis SJ, Schneider K, Li FP, Fraumeni J, Garber JE, Syngal S
Genet Med 2011 Jul;13(7):651-7. doi: 10.1097/GIM.0b013e31821628b6. PMID: 21552135Free PMC Article

Diagnosis

Giacomazzi J, Selistre SG, Rossi C, Alemar B, Santos-Silva P, Pereira FS, Netto CB, Cossio SL, Roth DE, Brunetto AL, Zagonel-Oliveira M, Martel-Planche G, Goldim JR, Hainaut P, Camey SA, Ashton-Prolla P
Cancer 2013 Dec 15;119(24):4341-9. Epub 2013 Oct 7 doi: 10.1002/cncr.28346. [Epub ahead of print] PMID: 24122735
Sorrell AD, Espenschied CR, Culver JO, Weitzel JN
Mol Diagn Ther 2013 Feb;17(1):31-47. doi: 10.1007/s40291-013-0020-0. PMID: 23355100Free PMC Article
Fresneau B, Brugières L, Caron O, Moutel G
J Genet Couns 2013 Jun;22(3):315-22. Epub 2012 Dec 12 doi: 10.1007/s10897-012-9556-0. [Epub ahead of print] PMID: 23233110
Magnusson S, Gisselsson D, Wiebe T, Kristoffersson U, Borg Å, Olsson H
Pediatr Blood Cancer 2012 Nov;59(5):846-53. Epub 2012 May 31 doi: 10.1002/pbc.24223. [Epub ahead of print] PMID: 22653678
Masciari S, Dewanwala A, Stoffel EM, Lauwers GY, Zheng H, Achatz MI, Riegert-Johnson D, Foretova L, Silva EM, Digianni L, Verselis SJ, Schneider K, Li FP, Fraumeni J, Garber JE, Syngal S
Genet Med 2011 Jul;13(7):651-7. doi: 10.1097/GIM.0b013e31821628b6. PMID: 21552135Free PMC Article

Therapy

Mosleh O, Tabori U, Bartels U, Huang A, Schechter T, Bouffet E
Pediatr Hematol Oncol 2013 Aug;30(5):386-91. Epub 2013 Jan 9 doi: 10.3109/08880018.2012.756089. [Epub ahead of print] PMID: 23301664
Fresneau B, Brugières L, Caron O, Moutel G
J Genet Couns 2013 Jun;22(3):315-22. Epub 2012 Dec 12 doi: 10.1007/s10897-012-9556-0. [Epub ahead of print] PMID: 23233110
Magnusson S, Gisselsson D, Wiebe T, Kristoffersson U, Borg Å, Olsson H
Pediatr Blood Cancer 2012 Nov;59(5):846-53. Epub 2012 May 31 doi: 10.1002/pbc.24223. [Epub ahead of print] PMID: 22653678
Heymann S, Delaloge S, Rahal A, Caron O, Frebourg T, Barreau L, Pachet C, Mathieu MC, Marsiglia H, Bourgier C
Radiat Oncol 2010 Nov 8;5:104. doi: 10.1186/1748-717X-5-104. [Epub ahead of print] PMID: 21059199Free PMC Article
Dickens DS, Dothage JA, Heideman RL, Ballard ET, Jubinsky PT
J Pediatr Hematol Oncol 2005 Jan;27(1):46-9. PMID: 15654279

Prognosis

Sorrell AD, Espenschied CR, Culver JO, Weitzel JN
Mol Diagn Ther 2013 Feb;17(1):31-47. doi: 10.1007/s40291-013-0020-0. PMID: 23355100Free PMC Article
Magnusson S, Gisselsson D, Wiebe T, Kristoffersson U, Borg Å, Olsson H
Pediatr Blood Cancer 2012 Nov;59(5):846-53. Epub 2012 May 31 doi: 10.1002/pbc.24223. [Epub ahead of print] PMID: 22653678
Heymann S, Delaloge S, Rahal A, Caron O, Frebourg T, Barreau L, Pachet C, Mathieu MC, Marsiglia H, Bourgier C
Radiat Oncol 2010 Nov 8;5:104. doi: 10.1186/1748-717X-5-104. [Epub ahead of print] PMID: 21059199Free PMC Article
Lammens CR, Aaronson NK, Wagner A, Sijmons RH, Ausems MG, Vriends AH, Ruijs MW, van Os TA, Spruijt L, Gómez García EB, Kluijt I, Nagtegaal T, Verhoef S, Bleiker EM
J Clin Oncol 2010 Jun 20;28(18):3008-14. Epub 2010 May 17 doi: 10.1200/JCO.2009.27.2112. [Epub ahead of print] PMID: 20479422
Evans DG, Lunt P, Clancy T, Eeles R
Fam Cancer 2010 Mar;9(1):65-9. Epub 2009 Apr 30 doi: 10.1007/s10689-009-9245-9. [Epub ahead of print] PMID: 19404774

Clinical prediction guides

Magnusson S, Gisselsson D, Wiebe T, Kristoffersson U, Borg Å, Olsson H
Pediatr Blood Cancer 2012 Nov;59(5):846-53. Epub 2012 May 31 doi: 10.1002/pbc.24223. [Epub ahead of print] PMID: 22653678
Villani A, Tabori U, Schiffman J, Shlien A, Beyene J, Druker H, Novokmet A, Finlay J, Malkin D
Lancet Oncol 2011 Jun;12(6):559-67. Epub 2011 May 19 doi: 10.1016/S1470-2045(11)70119-X. [Epub ahead of print] PMID: 21601526
Herbert BS, Chanoux RA, Liu Y, Baenziger PH, Goswami CP, McClintick JN, Edenberg HJ, Pennington RE, Lipkin SM, Kopelovich L
Oncotarget 2010 Oct;1(6):405-22. PMID: 21311097Free PMC Article
Heymann S, Delaloge S, Rahal A, Caron O, Frebourg T, Barreau L, Pachet C, Mathieu MC, Marsiglia H, Bourgier C
Radiat Oncol 2010 Nov 8;5:104. doi: 10.1186/1748-717X-5-104. [Epub ahead of print] PMID: 21059199Free PMC Article
Mirzayans R, Andrais B, Scott A, Paterson MC, Murray D
J Cell Physiol 2010 Apr;223(1):57-67. doi: 10.1002/jcp.22002. PMID: 20039273

Recent systematic reviews

Madge SN, Tumuluri K, Strianese D, Bonavolonta P, Wilcsek G, Dodd TJ, Selva D
Ophthalmology 2010 Mar;117(3):606-14. Epub 2009 Dec 22 doi: 10.1016/j.ophtha.2009.08.017. [Epub ahead of print] PMID: 20022639

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