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BRCA1 and BRCA2 Mutation Testing

BRCA1 and BRCA2 are human genes that belong to a class of genes known as tumour suppressors. Mutation of these genes has been linked to hereditary breast and ovarian cancer
A woman's risk of developing breast and/or ovarian cancer is greatly increased if she inherits a BRCA1 or BRCA2 mutation. Men with BRCA mutations also have an increased risk of breast cancer and other cancers.
The detection of BRCA mutations is important not only for prognostic purposes but also for treatment choice. PARP inhibitors target Poly (ADP-Ribose) Polymerase (PARP), a protein which normal cells use to repair genetic injuries. Cancer cells also use this protein to repair their own DNA damage. Inhibiting this action allows chemotherapy and radiation to do its job against cancers resulting from genetic mutation. Studies on PARP inhibitors in BRCA mutated cancers has shown significant response.

BRCA1

The BRCA1 gene is located on chromosome 17. Mutations of this gene are frequently associated with a significant increase in the risk of breast cancer, as well as ovarian, fallopian tube and prostate cancers. BRCA1 is a tumour suppressor gene, i.e. when its function is diminished or lost in a cell there is higher probability that the cell will become malignant. The protein product of the normal BRCA1 gene is involved in DNA damage repair and regulation of transcription, as well as other functions.

Certain variations of the BRCA1 gene lead to an increased risk for breast cancer. Researchers have identified more than 600 mutations in the BRCA1 gene, many of which are associated with an increased risk of cancer.

These mutations can be changes in one or a small number of DNA base pairs (the building blocks of DNA), and can be identified with PCR and DNA sequencing.
A mutated BRCA1 gene usually makes a protein that does not function properly because it is abnormally short ("truncated"). Researchers believe that the defective BRCA1 protein is unable to help fix mutations that occur in other genes. These defects accumulate and may allow cells to grow and divide uncontrollably to form a tumour.

In some cases, large segments of the DNA sequence of BRCA1 are rearranged. These large segments, also called large rearrangements, can be a deletion or a duplication of one or several exons in the gene.

BRCA2

Although the structures of the BRCA1 and BRCA2 genes are very different, their functions appear to be similar. Like BRCA1, the protein product of BRCA2 is involved in the repair of chromosomal damage and belongs to a class of genes known as tumour suppressor genes. Tumour suppressor genes regulate the cycle of cell division by keeping cells from growing and dividing too rapidly or in an uncontrolled way.

The BRCA2 gene is located on chromosome 13.

BRCA mutation testing at Source BioScience

Source BioScience provides BRCA mutation testing using next generation sequencing, rtPCR and multiplex ligation dependent probe amplification technology (MPLA).

For further details, please contact us at Pharma.

References:

• Ford D et al (1998) Genetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 genes in breast cancer families. The Breast Cancer Linkage Consortium. Am J Hum Genet 62:676-89.
• Starita LM and Parvin JD (2003). "The multiple nuclear functions of BRCA1: transcription, ubiquitination and DNA repair". Current Opinion in Cell Biology 15 (3): 345-350.
• Boulton SJ (2006). "Cellular functions of the BRCA tumour-suppressor proteins". Biochemical Society Transactions 34 (5): 633-645.
• Mazoyer S (2005). "Genomic rearrangements in the BRCA1 and BRCA2 genes". Hum Mutat. 25 (5): 415-22.
• Barrois M et al (2004). "Real-time PCR-based gene dosage assay for detecting BRCA1 rearrangements in breast-ovarian cancer families". Clin Genet. 65 (2): 131-6.
• Hogervorst FB et al (2003). "Large genomic deletions and duplications in the BRCA1 gene identified by a novel quantitative method". Cancer Res. 63 (7): 1449-53.
• Casilli F et al (2002). "Rapid detection of novel BRCA1 rearrangements in high-risk breast-ovarian cancer families using multiplex PCR of short fluorescent fragments". Hum Mutat. 20 (3): 218-26.
• Rouleau E et al (2007). "High-resolution oligonucleotide array-CGH applied to the detection and characterization of large rearrangements in the hereditary breast cancer gene BRCA1". Clin Genet. 72 (3): 199-207.