PALB2

About PALB2

PALB2 Partner and Localizer of BRCA2 on chromosome 16p12.2 encodes a protein that links BRCA1 and BRCA2 at sites of DNA damage and stabilizes BRCA2, enabling it to load RAD51 and carry out homologous recombination repair of DNA double strand breaks. Germline PALB2 variants are inherited in an autosomal dominant pattern and confer a substantially increased lifetime risk of breast cancer, approaching that of BRCA2 in some studies, as well as increased risks of pancreatic cancer and, to a lesser degree, ovarian cancer and male breast cancer. PALB2 is now regarded as one of the major breast cancer susceptibility genes after BRCA1 and BRCA2, and it was identified in 2006. Multigene panel testing for hereditary breast cancer routinely includes PALB2 along with BRCA1, BRCA2, TP53, PTEN, CDH1, ATM, and CHEK2. PALB2 deficient cancers share the BRCAness phenotype, showing sensitivity to platinum chemotherapy and PARP inhibitors. Inheriting pathogenic variants in both copies of PALB2 causes Fanconi anemia complementation group N, a severe form with bone marrow failure and early childhood cancers. Other homologous recombination genes included on hereditary cancer panels include RAD51C, RAD51D, BRIP1, and BARD1, with varying degrees of breast and ovarian cancer risk.