PALB2 c.1676A > G (rs152451A/G) and c.2993C > T (rs45551636C/T) variants were significantly associated with increased BC risk only in cases with a strong family history of BC (OR = 1.9 [CI 95% 1.3-2.8] p < 0.01 and OR = 3.3 [CI 95% 1.4-7.3] p < 0.01, respectively).
As PALB2-deficient tumors were shown to be sensitive to Poly(ADP-ribose) Polymerase (PARP) inhibitors, our study has implications for newly developed, favorable treatment options in familial breast cancer.
Given this mutation prevalence and risk, consideration might be given to clinical testing of PALB2 by complete genomic sequencing for familial breast cancer patients with wild-type sequences at BRCA1 and BRCA2.
Given this mutation prevalence and risk, consideration might be given to clinical testing of PALB2 by complete genomic sequencing for familial breast cancer patients with wild-type sequences at BRCA1 and BRCA2.
Hence, our approach allowed us to specify BC relative risks associated with deleterious-predicted variants in PALB2, ATM and CHEK2 and to add MAST1, POLH, RTEL1 and FANCI to the list of DNA repair genes possibly involved in BC susceptibility.
Here we show, by screening for PALB2 mutations in Finland that a frameshift mutation, c.1592delT, is present at significantly elevated frequency in familial breast cancer cases compared with ancestry-matched population controls.
Here we show, by screening for PALB2 mutations in Finland that a frameshift mutation, c.1592delT, is present at significantly elevated frequency in familial breast cancer cases compared with ancestry-matched population controls.
Heterozygous mutations in the PALB2hereditary breast cancer predisposition gene impact on the three-dimensional nuclear organization of patient-derived cell lines.
In five patients (5 of 83; 6% of cohort), we detected causative pathogenic variants in established hereditary breast cancer susceptibility genes (i.e., PALB2, CHEK2, ATM).
Loss-of-function mutations in PALB2 are an important cause of hereditary breast cancer, with respect both to the frequency of cancer-predisposing mutations and to the risk associated with them.
Loss-of-function mutations in PALB2 are an important cause of hereditary breast cancer, with respect both to the frequency of cancer-predisposing mutations and to the risk associated with them.