Analysis of <i>PALB2</i> Gene in <i>BRCA1</i>/<i>BRCA2</i> Negative Spanish Hereditary Breast/Ovarian Cancer Families with Pancreatic Cancer Cases

<div><p>Background</p><p>The <i>PALB2</i> gene, also known as <i>FANCN</i>, forms a bond and co-localizes with BRCA2 in DNA repair. Germline mutations in <i>PALB2</i> have been identified in approximately 1% of familial breast cancer and 3–4% of familial pancreatic cancer. The goal of this study was to determine the prevalence of <i>PALB2</i> mutations in a population of <i>BRCA1/BRCA2</i> negative breast cancer patients selected from either a personal or family history of pancreatic cancer.</p><p>Methods</p><p>132 non-<i>BRCA1/BRCA2</i> breast/ovarian cancer families with at least one pancreatic cancer case were included in the study. <i>PALB2</i> mutational analysis was performed by direct sequencing of all coding exons and intron/exon boundaries, as well as multiplex ligation-dependent probe amplification.</p><p>Results</p><p>Two <i>PALB2</i> truncating mutations, the c.1653T>A (p.Tyr551Stop) previously reported, and c.3362del (p.Gly1121ValfsX3) which is a novel frameshift mutation, were identified. Moreover, several <i>PALB2</i> variants were detected; some of them were predicted as pathological by bioinformatic analysis. Considering truncating mutations, the prevalence rate of our population of <i>BRCA1/2</i>-negative breast cancer patients with pancreatic cancer is 1.5%.</p><p>Conclusions</p><p>The prevalence rate of <i>PALB2</i> mutations in non-<i>BRCA1/BRCA2</i> breast/ovarian cancer families, selected from either a personal or family pancreatic cancer history, is similar to that previously described for unselected breast/ovarian cancer families. Future research directed towards identifying other gene(s) involved in the development of breast/pancreatic cancer families is required.</p></div

Pedigrees of the families carrying the mutations.

<p>a) c.1653T>A (p.Tyr551Stop); b) c.3362del (p.Glu1121ValfsX3). Cancer diagnoses are indicated in affected patients; in brackets the age at diagnosis or exitus. The <i>arrow</i> indicates the index case analyzed. <i>BC</i> breast cancer, <i>PC</i> Pancreatic Cancer, <i>CCR</i> Colorectal cancer, <i>CNS</i> central nervous system cancer.</p

<i>BRCA1/BRCA2</i> mutation-negative Spanish high risk breast/ovarian cancer families with pancreatic cancer cases.

<p>BC: Breast cancer; PC: Pancreatic cancer; OC: Ovarian cancer; BiOC: Bilateral Ovarian cancer; PrC: Prostate cancer; MBC: Male Breast cancer; BiBC: Bilateral Breast Cancer; CCR: Colorectal cancer; FDR: First degree relative; SDR: Second degree relative.</p

Overview of literature on role of <i>PALB2</i> mutations in FPC and in BC families affected by PC (BC-PC families).

<p>BC (breast cancer); PC (pancreatic cancer); FPC (familial pancreatic cancer); PrC (prostate cancer).</p

Additional file 2: of Male breast cancer in BRCA1 and BRCA2 mutation carriers: pathology data from the Consortium of Investigators of Modifiers of BRCA1/2

List of local ethics committees that granted approval for the access and use of the data in present study. (DOCX 23 kb