Background: The PALB2 gene encodes a protein that plays a crucial role in maintaining genomic integrity. Germline inactivating mutations in PALB2 are associated with an increased risk of breast and ovarian cancer. The prevalence and spectrum of recurrent PALB2 germline mutations in breast and ovarian cancer patients from Poland is not clearly defined.
Methods: PALB2 exons were amplified from 460 BRCA1/2-mutation negative women with familial breast and/or ovarian cancer and early-onset breast cancer using AmpliSeq technology and sequenced on an Ion Torrent PGM sequencer. In addition, eight selected variants were genotyped using TaqMan assays in 807 BRCA1/2-mutation negative breast cancer patients and 1690 healthy women.
Results: Two recurrent PALB2 mutations, c.172_175delTTGT and c.509_510delGA, were identified, along with one novel mutation, c.347insT. In total, PALB2 pathogenic mutations were detected in 7/460 (1.5%) patients. Furthermore, in breast and/or ovarian cancer patients, several single nucleotide variants (SNVs) were detected in the PALB2 coding region. In an additional group of 807 patients, eight (1%) carriers of two pathogenic mutations, c.172_175delTTGT (0.5%) and c.509_510delGA (0.5%), were identified. The c.509_510delGA mutation was not identified in healthy controls, while c.172_175delTTGT was identified in 4/1690 (0.24%) of control women.
Conclusions: Germline mutations in the PALB2 gene were observed at a frequency of approximately 1.5% in Polish breast and/or ovarian cancer patients. Our study confirms two recurrent PALB2 mutations; c.172_175delGA and c.509_510delGA.
Keywords: Hereditary breast and ovarian cancer; Next-generation sequencing; PALB2.