PALB2

The PALB2 gene provides instructions for making a protein called partner and localizer of BRCA2. As its name suggests, this protein interacts with the protein produced from the BRCA2 gene. These two proteins work together to mend broken strands of DNA, which prevents cells from accumulating genetic damage that can trigger them to divide uncontrollably. Because the PALB2 and BRCA2 proteins help control the rate of cell growth and division, they are described as tumor suppressors.

The PALB2 protein stabilizes the BRCA2 protein and anchors it to structures within the nucleus, allowing the BRCA2 protein to fix damaged DNA. Breaks in DNA can be caused by natural and medical radiation or other environmental exposures, and also occur when chromosomes exchange genetic material in preparation for cell division. By helping repair mistakes in DNA, the PALB2 and BRCA2 proteins play a critical role in maintaining the stability of a cell's genetic information.

breast cancer - associated with the PALB2 gene

About 10 mutations in the PALB2 gene have been identified in people with familial forms of breast cancer. These mutations occur in one copy of the gene in each cell and result in the production of an abnormally short version of the PALB2 protein. The defective protein cannot work with the BRCA2 protein to repair damaged DNA effectively. As defects accumulate in DNA, they can trigger cells to grow and divide uncontrollably and form a tumor. Researchers believe that PALB2 gene mutations may be associated with an approximately 2-fold increase in breast cancer risk.

other disorders - caused by mutations in the PALB2 gene

A condition called Fanconi anemia type N (FA-N) results from two mutated copies of the PALB2 gene in each cell. These mutations severely reduce or eliminate the activity of the PALB2 protein. Without enough of this protein, breaks in DNA are not repaired normally and genetic damage can build up over time. As a result, people with Fanconi anemia are prone to several types of cancer. In particular, Fanconi anemia type N increases the risk of several childhood cancers, including a rare form of kidney cancer called Wilms' tumor and a brain tumor called medulloblastoma. Additionally, people with Fanconi anemia experience bone marrow suppression, which causes an abnormal reduction in the number of red blood cells, white blood cells, and blood platelets made by the bone marrow. The reduced production of red blood cells causes the anemia characteristic of this disorder.

Genetics Home Reference provides information about Fanconi anemia, which is also associated with changes in the PALB2 gene.