Mary-Claire King may have wanted to honor Paul Broca by naming BRCA after him, but modern geneticists know the genes by their official names: "breast cancer 1, early onset" and "breast cancer 2, early onset." You may also hear "breast cancer susceptibility genes 1 and 2" or "hereditary breast cancer 1 and 2." With such similar names, you might think the two genes reside together on the same chromosome. That's not the case. The exact location of BRCA1 is 17q21; BRCA2 is 13q12.3. Here's what those numbers mean:
- The first number indicates the chromosome, which means BRCA1 can be found on chromosome 17, BRCA2 on chromosome 13.
- All chromosomes have a short arm, p, and a long arm, q, so both BRCA genes sit on the long arms of their respective chromosomes.
- When scientists stain chromosomes, genes appear as light- and dark-colored bands, which themselves are organized into regions. A two-digit number indicates the region followed by the band. A decimal reveals a sub-band. BRCA1, then, is located on region 2, band 1. BRCA2 is located on region 1, band 2, sub-band 3.
Even though BRCA1 and BRCA2 belong to different gene families, they both produce large proteins that participate in tumor suppression when they're working normally. The BRCA1 protein consists of 1,863 amino acids and BRCA2 of 3,418 amino acids [source: van der Groep]. The BRCA1 protein exerts its tumor suppression effects by collaborating with a number of other proteins to mend breaks in DNA. These BRCA1 protein complexes likely affect several DNA repair processes, including homologous recombination (swapping a sequence of nucleotides with another similar strand of DNA), nucleotide-excision repair (cutting out damaged DNA bases and pasting in new ones) and non-homologous end-joining (stitching a double-strand break back together). The BRCA2 protein also participates in DNA damage control, but appears to be much more limited. Scientists think the BRCA2 protein regulates the activity of a smaller number of companion proteins, including RAD51 and PALB2, to direct homologous recombination of damaged DNA.
Now imagine what would happen if you removed BRCA genes from a cell or threw a monkey wrench into their molecular machinery. Without their associated proteins, several DNA repair processes would cease to function and, over time, as cells were exposed to radiation or chemical agents, more and more defects would accumulate. These mutations would eventually cause cells to go wonky and become cancerous.
This is exactly what happens when BRCA genes become compromised. A mutation to one of the genes scrambles its instruction manual. As a result, the gene no longer has the ability to build correct versions of its related protein. The protein may be abnormally short or may not have the correct sequence of amino acids. These defective proteins can no longer participate in the DNA-repair process, which eventually leads to the proliferation of cells carrying damaged DNA. If these cells line the milk ducts of breast tissue, a lump or tumor, created by a mass of abnormal cells, may develop there. In addition to breast cancer, BRCA mutations can also lead to ovarian cancer, fallopian tube cancer, pancreatic cancer and prostate cancer.
Unfortunately, nature has found lots of ways to disrupt the BRCA genes. To date, scientists have identified more than 1,000 mutations in the BRCA1 gene and more than 800 mutations in the BRCA2 gene [sources: Genetics Home Reference, Genetics Home Reference]. And remember, these defective genes can be passed from one generation to the next, which means people who inherit the mutation carry it with them their whole lives. It sits in their cells, going unnoticed until a cancer develops or until someone takes steps to prevent that from happening. That's where genetic testing comes in.