Breast cancer and ovarian cancer (Breast and ovarian cancer) - BRCA1 and BRCA2 genes

Breast cancer is the most common cancer in women, of which an estimated one in 8 will develop throughout his life. It is the second leading cause of cancer death in women -after Lung cancer and the leading cause between 40 and 55 years. Ovarian cancer has a lower incidence with a risk to develop 1.5%, but is the first cause of death from gynecological cancer in the area despite being the third in frequency.

We found several genes that would be associated with an increased risk of breast cancer: BRCA1, BRCA2, CDH1, PTEN, STK11, TP53, AR, ATM, BARD1, BRIP1, CHEK2, DIRAS3, ERBB2, NBN, PALB2, RAD50 and RAD51 . Of these, the two most involved with hereditary breast cancer would be the tumor suppressor genes BRCA1 and BRCA2. In addition, BRCA1 mutations has been associated with the risk for developing inctremento of pancreatic carcinoma. Mutations in the BRCA2 gene has been associated with the risk of prostate, pancreatic and melanoma maligno.Las germline mutations in the BRCA1 gene truncating or inactivate cancer protein pose a risk of developing breast cancer before age 70 more than 85% and 30-40% in the case of ovarian cancer. Germline mutations in the BRCA2 gene, in turn, are associated with a 50% risk of breast cancer and 10-15% of ovarian cancer.

BRCA1 (Breast Cancer 1, early onset), located in the region 21 of the long arm of chromosome 17 (17q21) is constituted by 22 exons and encodes a nuclear phosphoprotein of 1,863 amino acids. This gene belongs to the class of genes called tumor suppressor genes. The BRCA1 protein encoded by this gene helps to prevent cells from growing too fast divide uncontrollably. For this purpose, the protein will repair the nuclear DNA in the nucleus interacting with proteins by codificacas and RAD51 genes BARD1. In addition, the BRCA1 protein is associated with RNA polymerase II through its C-terminal domain and interacts with histone deacetylase complex, involved in cell cycle progression in development processes and in regulating the transcription of several genes target genes including p21, GADD45, BAX, PCNA, cFos, Cdc34, PIN1, etc. They have been described over 1000 mutations in the BRCA1 gene. When there are mutations in the BRCA1 gene BRCA1 protein is not produced, an excessively short protein is produced, it no amino acid is changed, or part of it is removed. In these situations the BRCA1 protein can not perform the repair of cellular DNA.

BRCA2 (Breast Cancer 2, early onset), located in the region 12.3 of the long arm of chromosome 13 (13q12.3), encodes a protein of 3418 amino acids containing 8 repeats BRC. This gene also belongs to the class of genes called tumor suppressor genes, and as with other genes of this class, the BRCA2 protein helps prevent cells from growing too fast divide uncontrollably, involved in repair DNA. This protein interacts with other proteins, such as proteins RAD51 and PALB2 for repairing nuclear DNA. BRC BRCA2 protein repeats are conserved motifs of about 30 amino acids each, crucial for interaction with RAD51. The function of both proteins, BRCA2 and RAD51, depends on their mutual interaction. Therefore, BRCA2, RAD51 after interacting with, plays a key role in DNA repair by homologous recombination, constituting a key role in maintaining the stability of the genome. They have been described over 800 mutations in the BRCA2 gene. Many of these mutations insert or delete a small number of nucleotides in the gene. These genetic changes, altered protein synthesized, so that it is unable to repair damaged DNA.

The proteins encoded by two genes, BRCA1 and BRCA2 are therefore involved in maintaining genome integrity by participating in processes like DNA repair, cell cycle control and regulation control cell division. The presence of mutations in the coding regions of each of these genes can cause changes in the structure of the resultant protein, which results in loss of function and therefore generates an increase of genomic instability increasing chance of developing ovarian cancer or breast.

Mutations of the BRCA1 and BRCA2 genes, present in the hereditary breast cancer is inherited as an autosomal dominant pattern, meaning that the presence of one altered copy of the gene in each cell is sufficient to increase the risk of this type of Cancer.

Tests in IVAMI: IVAMI performed in detecting mutations in BRCA1 (22 exons) and BRCA2 (26 exons), by PCR amplification followed by direct sequencing. For detecting insertions, duplications and deletions perform quantification by real time PCR [Real time qPCR].

Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).