Mutation analysis of BRCA1 and BRCA2 is conducted to assess the predisposition genetics of the patient to the development of breast and ovarian cancers. The genes BRCA1 and BRCA2 genes are the main responsible of most cases of hereditary predisposition to these patologie.Una part of the breast and ovarian cancers are so-called sporadic that random mutations are acquired during the course of life, and are not transmitted to offspring. A large percentage of cancers can be hereditary. It is estimated that about 14% of breast cancers and 10% of ovarian cancers are caused by recurrent mutations in BRCA1 tumors and BRCA2.I hereditary breast and ovarian applicants are caused by mutations in the germ line that can be transmitted by both parents, both boys and girls, in an autosomal dominant, that children have a 50% chance of inheriting the genetic susceptibility to the development of those cancers. People who inherit a germline mutation have been designed with a copy of the mutated gene. However it should be stressed that these individuals do not inherit cancer, but only the predisposition to develop cancer. Not all people who are carriers of the mutation develop malignant disease, although these mutations greatly increase the risk of developing cancer, this does not develop until the normal copy of the corresponding gene is not subject to change throughout life. Since each person inherits two copies of the same gene, it must incur a mutational event in each copy to suppress the function of that gene, the acquisition of a new mutation can then directly cause the onset of cancer. RISK STATISTICS
breast cancer
Following extensive studies of families at risk, it was found that women who have inherited mutations in BRCA1 or BRCA2 genes are likely to develop breast cancer in 87% of cases , compared with a 10% chance of non-mutation carriers. The inherited mutations in these genes result in a significant increase in women's risk of developing breast cancer at an early age (before menopause), thus representing a characteristic feature of inherited susceptibility. Recent studies have in fact demonstrated that more than half of women with mutations in BRCA genes develop breast cancer before age 50, with an average age of diagnosis of cancer aged 41.
ovarian tumors
The risk of ovarian cancer in case of occurrence of mutations in one of two genes in question, however, is between 44-60%, compared with 1% probability of non-carriers. Events
genetic susceptibility testing is also very useful for those women who have already developed breast cancer because, if carriers of BRCA mutations, are high risk of developing a new breast cancer or ovarian cancer. For example, it was found that women with BRCA1 mutations who have had breast cancer, risk of developing a new tumor in 64% of cases. Percentages are provided similar risk for ovarian cancer.
risk of other cancers
Recent studies have reported that inherited mutations of BRCA1 or BRCA2 genes significantly increase the risk of prostate cancer in men and colon cancer in both sexes. The risk of prostate cancer was estimated to be 3-4 times higher than the general population in humans BRCA mutation carriers, with a cumulative risk of '8% while the risk of colon cancer was estimated to be 4-5 times higher in both women and man, with a cumulative risk of 6%. INTERPRETATION OF RESULTS
Genetic testing determines whether a person has or without mutations in BRCA1 or BRCA2.Un positive result means that you have identified one or more specific mutations, and therefore can be estimated in probabilistic terms the risk of developing cancer associated with that type of mutation. Not all women with mutations in BRCA1 or BRCA2 develop malignant disease, but the risk is high enough. Although the disease is rare for the male, a man who has the BRCA1 or BRCA2 mutations have a risk more to develop a cancer mammella.Un negative result means that no mutation was not found. However, it is important to note that a negative result does not mean that the patient has zero risk of developing breast or ovarian cancer, these women have the same cancer risk reported for the general population, this is because most of this kind of is expressed in sporadic cancers, for reasons still not well known.
FEATURES
BRCA1 and BRCA2 genes BRCA1 and BRCA2 tumor suppressor genes are located respectively on chromosome 17 and chromosome 13. In genetically predisposed persons, loss of function of tumor suppressor gene is due to events recurrent mutation at the level of that gene, resulting in the production of a protein anormale.Il BRCA1 gene contains 24 exons and has a size of about 5.6 Kb, while the BRCA2 gene comprises 27 exons and has a size of approximately 10 kb L ' analysis of hundreds of persons of different ethnic groups with a family history of breast or ovarian cancer showed the presence of more than 150 different mutations in this gene, most of which produce a protein tronca.Le recurrent mutations in this gene are the cause of most cases of hereditary breast and ovarian cancer.
ANALYSIS OF MUTATION Mutation analysis of the DNA is carried out initially operate a reaction enzymatic amplification of DNA, known as Polymerase Chain Reaction (PCR), which allows in vitro amplification of a specific region of the molecule, copying in various stages, to obtain millions of copie.In this manner is amplified the complete coding region and the intron region for each exon of the gene, then PCR products so obtained are sequenced through the use of an automatic sequencer in fluorescent technology. The sequence of each exon was confirmed by sequencing the opposite strand, and then is carried the 'Comparative analysis of two sequences with a reference sequence without BRCA mutations (wild type sequence) to inquire whether presence of mutation.
Summary information about the disease:
Frequency:
investigated
Gene: BRCA1, BRCA2
employed methods:
automated sequencing
Report: Technical Report
Informed consent: must
Prenatal Diagnosis:
Inheritance: autosomal dominant
Advice Genetic
necessary
Biological samples that you can run the test: blood samples in EDTA
2 ml 2 ug DNA
Federico Cesareo
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