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Partner and localizer of BRCA2 (PALB2), plays an important functional role in DNA damage repair. Recent studies indicate that germline mutations in PALB2 predispose individuals to a high risk of developing familial breast cancer. Therefore, comprehensive identification of PALB2 germline mutations is potentially important for understanding their roles in tumorigenesis and for testing their potential utility as clinical targets. Most of the previous studies of PALB2 have focused on familial breast cancer cases with normal/wild-type BRCA1 and BRCA2 (BRCAx). We hypothesize that PALB2 genetic mutations also exist in individuals with BRCA mutations (BRCA+). To test this hypothesis, PALB2 germline mutations were screened in 107 exome data sets collected from familial breast cancer families who were either BRCA1+ or BRCAx. Two novel heterozygous mutations predicted to alter the function of PALB2 were identified (c.2014G>C, p.E672Q and c.2993G>A, p.G998E). Notably, both of these mutations co-existed in BRCA1+ and BRCA1x families. These studies show that mutations in PALB2 can occur independent of the status of BRCA1 mutations, and they highlight the importance to include BRCA1+ families in PALB2 mutation screens.

In the present study, the dephosphorization of Fe-Ni-Si melt by CaO-saturated CaO-CaF2 slag was investigated, from which it was found that the dephosphorization efficiency increases as increasing the silicon content, meanwhile the increase rate becomes rapid when the silicon content is more than 10 mass pct. By analyzing the phase compositions of the dephosphorization slag of a high silicon Fe-Ni-Si melt, it was first found the dephosphorization products change with the silicon content. When Si contents are 10.5, 31.48, 34.71, and 43.15 mass pct, the de-P products are Ca2P2, Ca10+x Si12−2x P16, Ca4SiP4, and Ca10+x Si12−2x P16, as well as Ca4SiP4, respectively. The corresponding dephosphorization mechanism can be described as $$ (2x)({\text{CaO}}) + (x + 2y)[{\text{Si}}] + 2z[{\text{P}}] = x({\text{SiO}}_{2} ) + 2({\text{Ca}}_{x} {\text{Si}}_{y} {\text{P}}_{z} ) $$ .

Background BRCA1 plays an essential role in maintaining genome stability. Inherited BRCA1 germline mutation (BRCA1+) is a determined genetic predisposition leading to high risk of breast cancer. While BRCA1+ induces breast cancer by causing genome instability, most of the knowledge is known about somatic genome instability in breast cancer cells but not germline genome instability. Methods Using the exome-sequencing method, we analyzed the genomes of blood cells in a typical BRCA1+ breast cancer family with an exon 13-duplicated founder mutation, including six breast cancer-affected and two breast cancer unaffected members. Results We identified 23 deleterious mutations in the breast cancer-affected family members, which are absent in the unaffected members. Multiple mutations damaged functionally important and breast cancer-related genes, including transcriptional factor BPTF and FOXP1, ubiquitin ligase CUL4B, phosphorylase kinase PHKG2, and nuclear receptor activator SRA1. Analysis of the mutations between the mothers and daughters shows that most mutations were germline mutation inherited from the ancestor(s) while only a few were somatic mutation generated de novo. Conclusion Our study indicates that BRCA1+ can cause genome instability with both germline and somatic mutations in non-breast cells.