Analysis of PALB2 gene in BRCA1/BRCA2 negative Spanish hereditary breast/ovarian cancer families with pancreatic cancer cases.
BACKGROUND
The PALB2 gene, also known as FANCN, forms a bond and co-localizes with BRCA2 in DNA repair. Germline mutations in PALB2 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 PALB2 mutations in a population of BRCA1/BRCA2 negative breast cancer patients selected from either a personal or family history of pancreatic cancer.


METHODS
132 non-BRCA1/BRCA2 breast/ovarian cancer families with at least one pancreatic cancer case were included in the study. PALB2 mutational analysis was performed by direct sequencing of all coding exons and intron/exon boundaries, as well as multiplex ligation-dependent probe amplification.


RESULTS
Two PALB2 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 PALB2 variants were detected; some of them were predicted as pathological by bioinformatic analysis. Considering truncating mutations, the prevalence rate of our population of BRCA1/2-negative breast cancer patients with pancreatic cancer is 1.5%.


CONCLUSIONS
The prevalence rate of PALB2 mutations in non-BRCA1/BRCA2 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.
Fundación Pública Galega de Medicina Xenómica-Servicio Galego de Saúde, Grupo de Medicina Xenómica-Universidade de Santiago de Compostela, Spanish Network on Rare Diseases (CIBERER), Instituto de Investigaciones Sanitarias de Santiago, Santiago de Compostela, A Coruña, Spain.
Ana
A
Blanco
Miguel
M
de la Hoya
Ana
A
Osorio
Orland
O
Diez
María Dolores
MD
Miramar
Mar
M
Infante
Cristina
C
Martinez-Bouzas
Asunción
A
Torres
Adriana
A
Lasa
Gemma
G
Llort
Joan
J
Brunet
Begoña
B
Graña
Pedro
P
Perez Segura
María José
MJ
Garcia
Sara
S
Gutiérrez-Enríquez
Ángel
Á
Carracedo
María-Isabel
MI
Tejada
Eladio A
EA
Velasco
María-Teresa
MT
Calvo
Judith
J
Balmaña
Javier
J
Benitez
Trinidad
T
Caldés
Ana
A
Vega
D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000150:complications / Q000151:congenital* / Q000235:genetics; D019295:Computational Biology; D004252:DNA Mutational Analysis; D005190:Family; D000076164:Fanconi Anemia Complementation Group N Protein; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics; D010190:Pancreatic Neoplasms / Q000150:complications* / Q000235:genetics*; D010375:Pedigree; D013030:Spain; D025521:Tumor Suppressor Proteins / Q000235:genetics*
D019313:BRCA1 Protein; D024682:BRCA2 Protein; D000076164:Fanconi Anemia Complementation Group N Protein; D009687:Nuclear Proteins; C512790:PALB2 protein, human; D025521:Tumor Suppressor Proteins