BRCA2 gene


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BRCA2 gene

a tumor suppressor gene identified in 1995 on chromosome 13 at locus 13q12-q13; a large gene consisting of 27 exons distributed over 70 kb, encoding a protein of 3,418 amino acids. Carriers of germline mutations in BRCA2 have an increased risk, similar to that of those with BRCA1 mutations, of developing breast cancer and a moderately increased risk of ovarian cancer. BRCA2 families also exhibit an increased incidence of male breast, pancreatic, prostate, laryngeal, and ocular cancers.
See also: BRCA1 gene, carcinoma of the breast.

Familial clustering of breast cancer has long been recognized. Familial breast cancers are characterized by onset before age 45 and by occurrence in three or more close relatives and in members of more than one generation. About 5% of all breast cancers are due to the inheritance of dominant susceptibility genes, particularly BRCA1 and BRCA2. Whereas spontaneous mutations of the BRCA genes are uncommon, hundreds of inherited mutations have been discovered on each gene. The clinical significance of many of them is unknown. Because these are autosomal chromosomes, men as well as women can inherit and pass on the BRCA mutations. The histology of breast cancer in women with BRCA1 and BRCA2 mutations differs from that of sporadic cases. The proportion of medullary carcinomas is higher among BRCA1-associated breast cancers than among all breast cancers. BRCA1 and BRCA2 are tumor suppressor genes, inhibiting tumor development when functioning normally. Both are large genes, with a prodominance of two distinct mutations for BRCA1 and one for BRCA2. Despite the high penetrance of the mutant gene, not all carriers develop cancer. Hormonal, environmental, reproductive, and other genetic factors may influence penetrance. Estradiol increases cell proliferation and production of the BRCA1 gene expression. Observed mutations are distributed throughout the gene; the majority are insertions, deletions, or nonsense mutations. Two common changes (185delAG and 5382insC, in exons 2 and 20, respectively) account for approximatesly 19% of BRCA1 mutations. The former of these is present in about 1% of Ashkenazic Jews and is responsible for about 32% of familial breast cancer in Jews. It is also found in 13% of ovarian cancer patients with no family history of breast or ovarian cancer, and in 30% of those with family histories suggesting inherited disease. BRCA1 mutations cause a threefold increase in the risk of prostate cancer and, in people of both sexes, a fourfold increase in the risk of colon cancer. The BRCA2 6174delT mutation is estimated to be present in 1.3% of Ashkenazic Jews. The risk that a woman with a BRCA1 or BRCA2 gene mutation will develop breast cancer at some time in her life is believed to be 10-30%. In addition, 15-20% of women with the BRCA1 mutations will develop ovarian cancer. Although testing for BRCA genetic mutations is available, most authorities do not recommend routine screening except in women with a strong family history of cancer. Women found to have BRCA genetic mutations have been advised to begin breast self-examination at age 18 and regular annual physician examinations and mammograms at age 25. The benefit of radiologic screening must be weighed against the possible effect of radiation on the BRCA1 or BRCA2 allele. MRI has been recommended by some authorities for annual surveillance of women at high risk. There is insufficient evidence to support the belief that periodic screening of women at high risk of ovarian cancer with serum markers, transvaginal ultrasound, or pelvic examinations can reduce mortality from ovarian cancer. Tamoxifen has been shown to reduce the risk of breast cancer in genetically predisposed women by as much as 50%.

BRCA2 gene

(jēn)
A tumor suppressor gene identified in 1995 on chromosome 13 at locus 13q12-q13; a large gene consisting of 27 exons distributed over 70 kb, encoding a protein of 3418 amino acids; carriers of germline mutations in BRCA2 have an increased risk, similar to that of those with BRCA1 mutations, of developing breast cancer and a moderately increased risk of ovarian cancer; BRCA2 families also exhibit an increased incidence of male breast, pancreatic, prostate, laryngeal, and ocular cancers.
See also: BRCA1 gene, carcinoma of the breast

BRCA2 gene

A breast cancer gene found in a small number of patients with breast and ovarian cancers, and carried by some individuals who will develop breast cancer later in life.
See also: gene
References in periodicals archive ?
These findings remained similar regardless of whether mutations were in the BRCA1 or BRCA2 gene, and when controlled for body mass index and ethnicity.
The BRCA1 and BRCA2 genes, responsible for the majority of hereditary breast and ovarian cancers, he said, were discovered in 1994-1995 through global studies in families with multiple cases of breast and ovarian cancer.
Results of molecular analysis of the BRCA1 and BRCA2 gene sequences were registered in Excel[R] tables and mutation frequencies were subsequently defined.
Mutations identified in our series were not found earlier in Algerian patients with sporadic or heredity breast cancer except the large rearrangement involving the BRCA2 gene caused the deletion of exon 2 reported by [2] and the heterozygous germline BRCA1 c.
In the US, frustrated with Myriad Genetics' strict enforcement of its patent rights on BRCA1 and BRCA2 genes, the Association for Molecular Pathology, the American Civil Liberties Union, the Public Patent Foundation and a group of patients and clinicians brought a lawsuit in May, 2009, in the District Court of the Southern District of New York against the USPTO alleging that the USPTO should not have issued the patents to Myriad since human genes such as BRCA1/BRCA2 are products of nature, common to mankind and should not be the products of commerce.
The presence of the BRCA2 gene meant Michelle had an 80% risk of contracting breast cancer but, unlike others with the gene, she was told her risk of contracting ovarian cancer was less prevalent.
About one out of every 40 individuals of Ashkenazi Jewish ancestry has a mutation in the BRCA1 or BRCA2 gene, which is much higher than the general population.
Alison went to Birmingham Women's Hospital where she and her sister both tested positive for the BRCA2 gene.
Lead researcher Professor Ros Eeles, from the Institute of Cancer Research, in London, said: "Our study shows that men diagnosed with prostate cancer at a young age have a higher chance of carrying a faulty BRCA2 gene.
Still, according to the National Cancer Institute, women with an altered BRCA1 or BRCA2 gene are three to seven times more likely to develop breast cancer than women who don't have alterations in those genes.
They also studied tumor cells from women with a faulty BRCA2 gene whose cancers had become resistant to carboplatin.
Mutations in the BRCA1 or BRCA2 gene confer a significantly increased risk of breast and ovarian cancer.