p53 mutation – Li-Fraumeni Syndrome – Likelihood of Genetic or Hereditary conditions playing a role in Intergenerational incidence of Cancer
Reporter: Aviva Lev-Ari, PhD, RN
THIS ARTICLE IS RECOMMENDED READING TO ALL OUR e-Readers
because it is a REAL story of a high school student fighting Brain Cancer, glioblastoma multiforme (GBM)
it presents the FRONTIER OF GENOMICS, PRECISION MEDICINE, Interventional Radiology and Interventional ONCOLOGY at
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I was exposed to Li-Fraumeni Syndrome in the following article:
‘And yet, you try’ – A father’s quest to save his son
Other Names for This Condition
- Sarcoma family syndrome of Li and Fraumeni
- Sarcoma, breast, leukemia, and adrenal gland (SBLA) syndrome
- SBLA syndrome
LFS 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 sarcoma forms in soft tissues of the body, including muscle, tendons, fat, blood vessels, lymph vessels, nerves, and tissue around joints.
(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.
The CHEK2 and TP53 genes are associated with Li-Fraumeni syndrome.
More than half of all families with Li-Fraumeni syndrome have inherited mutations in the gene. TP53 is a tumor suppressor gene, which means that it normally helps control the growth and division of cells. Mutations in this gene can allow cells to divide in an uncontrolled way and form tumors. Other genetic and environmental factors are also likely to affect the risk of cancer in people with TP53 mutations.
A few families with cancers characteristic of Li-Fraumeni syndrome and Li-Fraumeni-like syndrome do not have TP53 mutations, but have mutations in the CHEK2 gene. Like the TP53 gene, CHEK2 is a tumor suppressor gene. Researchers are uncertain whether CHEK2 mutations actually cause these conditions or are merely associated with an increased risk of certain cancers (including breast cancer).
Li-Fraumeni syndrome is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to increase the risk of developing cancer. In most cases, an affected person has a parent and other family members with cancers characteristic of the condition.
Diagnosis and Management
These resources address the diagnosis or management of Li-Fraumeni syndrome:
References on LFS
Chompret A. The Li-Fraumeni syndrome. Biochimie. 2002 Jan;84(1):75-82.
Melean G, Sestini R, Ammannati F, Papi L. Genetic insights into familial tumors of the nervous system. Am J Med Genet C Semin Med Genet. 2004 Aug 15;129C(1):74-84. Review.
Moule RN, Jhavar SG, Eeles RA. Genotype phenotype correlation in Li-Fraumeni syndrome kindreds and its implications for management. Fam Cancer. 2006;5(2):129-33. 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.
Strong LC. General keynote: hereditary cancer: lessons from Li-Fraumeni syndrome. Gynecol Oncol. 2003 Jan;88(1 Pt 2):S4-7; discussion S11-3. Review.
Varley J. TP53, hChk2, and the Li-Fraumeni syndrome. Methods Mol Biol. 2003;222:117-29. Review.
Varley JM. Germline TP53 mutations and Li-Fraumeni syndrome. Hum Mutat. 2003 Mar;21(3):313-20. Review. Erratum in: Hum Mutat. 2003 May;21(5):551.
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.
de Jong MM, Nolte IM, te Meerman GJ, van der Graaf WT, Oosterwijk JC, Kleibeuker JH, Schaapveld M, de Vries EG. Genes other than BRCA1 and BRCA2 involved in breast cancer susceptibility. J Med Genet. 2002 Apr;39(4):225-42. Review.