A topological model of negative biofeedback on breast cancer by PALB2 gene
PALB2, also known as the partner and the localizer of BRCA2 is a tumor suppressor gene whose mutation has been resulted to breast cancer and also Fanconi's anaemia. SIFT, Polyphen2, I-mutant, pHD snp, SNP & GO, ALIGN GVGD, SNPs 3D were used to find the deletorious effects of mutation on the protein structure and function and these mutations are correlated with the 3D X-Ray crystallographyic structure available in the PDB. PALB2 (Partner And Localizer of BRCA2) binds to and colocalizes with BRCA2 in DNA repair. Germline mutations in PALB2 have been identified in approximately 1–2% of familial breast cancer and 3–4% of familial pancreatic cancer cases. The goal of this study was to evaluate the prevalence of PALB2 mutations in women with breast cancer without BRCA1/2 mutations who also had a personal or family history of pancreatic cancer. PALB2mutation analysis was performed in 94 non-BRCA1/2 breast cancer patients with a personal or family history of pancreatic cancer. Two truncating PALB2 mutations, c.3549C>CA and c.2962C>CT, were identified resulting in a mutation prevalence of 2.1%. Two novel PALB2 missense variants were also found, one of which was deemed potentially deleterious. The prevalence rate of PALB2 mutations in a non-BRCA1/2 breast cancer population specifically selected for a family history of pancreatic cancer does not appear to be significantly increased compared to that observed in other breast cancer populations studied thus far. Further evaluation is needed to determine the prevalence of PALB2 mutations and the clinical utility of such testing in those individuals affected with both breast and pancreatic cancers.