Li-Fraumeni syndrome
Encyclopedia
Li-Fraumeni syndrome is an extremely rare autosomal dominant hereditary disorder. It is named after Frederick Pei Li
and Joseph F. Fraumeni, Jr., the American physicians who first recognized and described the syndrome. Li-Fraumeni syndrome greatly increases susceptibility to cancer
. The syndrome is linked to germline mutations of the p53
tumor suppressor gene
, which normally helps control cell growth. Mutations can be inherited or can arise de novo early in embryogenesis or in one of the parent's germ cells.
Persons with LFS are at risk for a wide range of malignancies, with particularly high occurrences of breast cancer, brain tumors, acute leukemia, soft tissue sarcoma
s, bone sarcomas, and adrenal cortical carcinoma.
Genetic counseling
and genetic testing
are used to confirm that somebody has this gene mutation. Once such a person is identified, early and regular screenings for cancer are recommended for him or her. If caught early the cancers can often be successfully treated. Unfortunately, people with Li-Fraumeni are likely to develop another primary malignancy at a future time.
Frederick Pei Li
Frederick Pei Li is an Chinese-American physician.Frederick Pei Li was born in Canton, China , and raised in New York City where his parents operated a Chinese restaurant. He is a pioneer researcher of cancer among genetically predisposed families described as Li-Fraumeni syndrome. He received a...
and Joseph F. Fraumeni, Jr., the American physicians who first recognized and described the syndrome. Li-Fraumeni syndrome greatly increases susceptibility to cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
. The syndrome is linked to germline mutations of the p53
P53
p53 , is a tumor suppressor protein that in humans is encoded by the TP53 gene. p53 is crucial in multicellular organisms, where it regulates the cell cycle and, thus, functions as a tumor suppressor that is involved in preventing cancer...
tumor suppressor gene
Tumor suppressor gene
A tumor suppressor gene, or anti-oncogene, is a gene that protects a cell from one step on the path to cancer. When this gene is mutated to cause a loss or reduction in its function, the cell can progress to cancer, usually in combination with other genetic changes.-Two-hit hypothesis:Unlike...
, which normally helps control cell growth. Mutations can be inherited or can arise de novo early in embryogenesis or in one of the parent's germ cells.
Persons with LFS are at risk for a wide range of malignancies, with particularly high occurrences of breast cancer, brain tumors, acute leukemia, soft tissue sarcoma
Sarcoma
A sarcoma is a cancer that arises from transformed cells in one of a number of tissues that develop from embryonic mesoderm. Thus, sarcomas include tumors of bone, cartilage, fat, muscle, vascular, and hematopoietic tissues...
s, bone sarcomas, and adrenal cortical carcinoma.
Characteristics
What makes Li-Fraumeni Syndrome unusual is that- several kinds of cancer are involved,
- cancer often appears at a young age
- cancer often appears several times throughout the life of an affected person.
Diagnosis and treatment
Li-Fraumeni Syndrome is diagnosed if the following three criteria are met:- the patient has been diagnosed with a sarcoma at a young age (below 45),
- a first-degree relative has been diagnosed with any cancer at a young age (below 45),
- and another first-degree or a second-degree relative has been diagnosed with any cancer at a young age (below 45) or with a sarcoma at any age.
Genetic counseling
Genetic counseling
Genetic counseling or traveling is the process by which patients or relatives, at risk of an inherited disorder, are advised of the consequences and nature of the disorder, the probability of developing or transmitting it, and the options open to them in management and family planning...
and genetic testing
Genetic testing
Genetic testing is among the newest and most sophisticated of techniques used to test for genetic disorders which involves direct examination of the DNA molecule itself. Other genetic tests include biochemical tests for such gene products as enzymes and other proteins and for microscopic...
are used to confirm that somebody has this gene mutation. Once such a person is identified, early and regular screenings for cancer are recommended for him or her. If caught early the cancers can often be successfully treated. Unfortunately, people with Li-Fraumeni are likely to develop another primary malignancy at a future time.
Pathology
- LFS1: The TP53 (tumor suppressor geneTumor suppressor geneA tumor suppressor gene, or anti-oncogene, is a gene that protects a cell from one step on the path to cancer. When this gene is mutated to cause a loss or reduction in its function, the cell can progress to cancer, usually in combination with other genetic changes.-Two-hit hypothesis:Unlike...
p53P53p53 , is a tumor suppressor protein that in humans is encoded by the TP53 gene. p53 is crucial in multicellular organisms, where it regulates the cell cycle and, thus, functions as a tumor suppressor that is involved in preventing cancer...
) normally assists in the control of cell division and growth through action on the normal cell cycleCell cycleThe cell cycle, or cell-division cycle, is the series of events that takes place in a cell leading to its division and duplication . In cells without a nucleus , the cell cycle occurs via a process termed binary fission...
. TP53 assists in repair or destruction of "bad" DNA before it can enter the normal cell cycle, thus preventing abnormal and/or cancerCancerCancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
ous growth of cells. MutationMutationIn molecular biology and genetics, mutations are changes in a genomic sequence: the DNA sequence of a cell's genome or the DNA or RNA sequence of a virus. They can be defined as sudden and spontaneous changes in the cell. Mutations are caused by radiation, viruses, transposons and mutagenic...
s of TP53 prevent this normal function and allow damaged cells to divide and grow in an uncontrolled, unchecked manner forming tumors (cancers). TP53 mutations have been primarily implicated in Li-Fraumeni.
- LFS2: A variant of Li-Fraumeni does not have a mutation in TP53 but instead has mutation of the CHEK2CHEK2CHEK2 is the official symbol for the human gene CHK2 checkpoint homolog. It is located on the long arm of chromosome 22.-Function:The protein encoded by this gene, CHK2 a protein kinase that is activated in response to DNA damage and is involved in cell cycle arrest.In response to DNA damage and...
(or CHK2) gene. CHK2 is also a tumor suppressor geneTumor suppressor geneA tumor suppressor gene, or anti-oncogene, is a gene that protects a cell from one step on the path to cancer. When this gene is mutated to cause a loss or reduction in its function, the cell can progress to cancer, usually in combination with other genetic changes.-Two-hit hypothesis:Unlike...
. The complete implication of this mutation is not known, but CHK2 regulates the action of p53. CHK2 is activated by ATM which detects DNA damage, and in this way DNA damage information can be conveyed to p53 to indirectly arrest the cell cycle at that point for DNA repair to be able to take place or to cause apoptosis (programmed cell death).
External links
- Li-Fraumeni syndrome, in the National Library of Medicine Genetics Home Reference (an introduction to the disease)
- Li-Fraumeni Syndrome by Katherine A Schneider and Frederick Li, in GeneReviews, a section of GeneTests, published online by the University of WashingtonUniversity of WashingtonUniversity of Washington is a public research university, founded in 1861 in Seattle, Washington, United States. The UW is the largest university in the Northwest and the oldest public university on the West Coast. The university has three campuses, with its largest campus in the University...
with funds from the National Institutes of HealthNational Institutes of HealthThe National Institutes of Health are an agency of the United States Department of Health and Human Services and are the primary agency of the United States government responsible for biomedical and health-related research. Its science and engineering counterpart is the National Science Foundation... - Li-Fraumeni syndrome; LFS1, entry in Online Mendelian Inheritance in Man (OMIM), published by Johns Hopkins UniversityJohns Hopkins UniversityThe Johns Hopkins University, commonly referred to as Johns Hopkins, JHU, or simply Hopkins, is a private research university based in Baltimore, Maryland, United States...
and the National Institutes of HealthNational Institutes of HealthThe National Institutes of Health are an agency of the United States Department of Health and Human Services and are the primary agency of the United States government responsible for biomedical and health-related research. Its science and engineering counterpart is the National Science Foundation... - European Li-Fraumeni Families Foundation ELFF