title: BRCA1 allele-specific expression in genetic predisposed breast/ovarian cancer.
abstract: Germline allele specific expression (ASE), resulting in a lowered expression of one of the BRCA1 alleles, has been described as a possible predisposition marker in Hereditary Breast or Ovarian Cancer (HBOC), usable for molecular diagnosis in HBOC. The main objective of this prospective case-control study was to compare the proportion of ASE between controls without familial history of breast or ovarian cancer, and HBOC cases without BRCA1 or BRCA2 deleterious mutation. BRCA1 ASE evaluated on three SNPs among controls and HBOC patients without deleterious mutation were assessed by pyrosequencing. The allelic ratios and the proportion of ASE were compared between controls and cases using a Student's t test and a Fisher exact test, respectively. The linearity and reproducibility of the ASE dosage was demonstrated with R2> 0.99 and a coefficient of variation below 10 %, and ASE was detected in two positive controls harbouring BRCA1 truncated mutations. In the heterozygote population, composed of 99/264 controls (37.5 %) and 96/227 patients (42.3 %), we detected a 5 % ASE without truncated mutations, in each population. We failed to detect any significant difference of ASE between controls and patients. So far, BRCA1 Allelic specific expression is not usable in routine diagnosis as a possible predisposition marker in HBOC patients except for the detection of truncated mutations.
authors: Laboratoire de Biologie et Génétique du Cancer - Centre Normand de Génomique Médicale et Médecine Personnalisée, Centre François Baclesse, 3 avenue du général Harris, 14076, Caen Cedex 05, France.
authors: Estelle
authors: E
authors: Jamard
authors: Laboratoire de Biologie et Génétique du Cancer - Centre Normand de Génomique Médicale et Médecine Personnalisée, Centre François Baclesse, 3 avenue du général Harris, 14076, Caen Cedex 05, France.
authors: Bertrand
authors: B
authors: Volard
authors: Service de recherche clinique, Centre François Baclesse, Caen, France.
authors: Audrey Emmanuelle
authors: AE
authors: Dugué
authors: Laboratoire de Biologie et Génétique du Cancer - Centre Normand de Génomique Médicale et Médecine Personnalisée, Centre François Baclesse, 3 avenue du général Harris, 14076, Caen Cedex 05, France.
authors: Angelina
authors: A
authors: Legros
authors: Service de recherche clinique, Centre François Baclesse, Caen, France.
authors: Alexandra
authors: A
authors: Leconte
authors: Service de recherche clinique, Centre François Baclesse, Caen, France.
authors: Bénédicte
authors: B
authors: Clarisse
authors: Laboratoire de Biologie et Génétique du Cancer - Centre Normand de Génomique Médicale et Médecine Personnalisée, Centre François Baclesse, 3 avenue du général Harris, 14076, Caen Cedex 05, France.
authors: Grégoire
authors: G
authors: Davy
authors: Consultation d'oncogénétique, Centre François Baclesse, Caen, France.
authors: Florence
authors: F
authors: Polycarpe
authors: Consultation d'oncogénétique, CHU, Rennes, France.|Consultation d'oncogénétique, Centre Eugène Marquis, Rennes, France.
authors: Catherine
authors: C
authors: Dugast
authors: Consultation d'oncogénétique, CHU, Rennes, France.|Consultation d'oncogénétique, Centre Eugène Marquis, Rennes, France.
authors: Caroline
authors: C
authors: Abadie
authors: Inserm U1079, Université de Médecine Pharmacie, Rouen, France.|Consultation d'oncogénétique, CHU, Rouen, France.
authors: Thierry
authors: T
authors: Frebourg
authors: Inserm U1079, Université de Médecine Pharmacie, Rouen, France.|Consultation d'oncogénétique, CHU, Rouen, France.
authors: Julie
authors: J
authors: Tinat
authors: Consultation d'oncogénétique, Centre Henri Becquerel, Rouen, France.
authors: Isabelle
authors: I
authors: Tennevet
authors: Consultation d'oncogénétique, Centre Hospitalier, Le Havre, France.
authors: Valérie
authors: V
authors: Layet
authors: Service de recherche clinique, Centre François Baclesse, Caen, France.|Université de Caen-Normandie -UMR-S1077, Caen, France.|Inserm- U1086, Caen, France.|Department of Oncology, CHU de Caen, Caen, France.
authors: Florence
authors: F
authors: Joly
authors: Laboratoire de Biologie et Génétique du Cancer - Centre Normand de Génomique Médicale et Médecine Personnalisée, Centre François Baclesse, 3 avenue du général Harris, 14076, Caen Cedex 05, France.|Inserm U1079, Université de Médecine Pharmacie, Rouen, France.
authors: Laurent
authors: L
authors: Castéra
authors: Inserm U1079, Université de Médecine Pharmacie, Rouen, France.|Consultation d'oncogénétique, Centre François Baclesse, Caen, France.
authors: Pascaline
authors: P
authors: Berthet
authors: Laboratoire de Biologie et Génétique du Cancer - Centre Normand de Génomique Médicale et Médecine Personnalisée, Centre François Baclesse, 3 avenue du général Harris, 14076, Caen Cedex 05, France.|Inserm U1079, Université de Médecine Pharmacie, Rouen, France.
authors: Dominique
authors: D
authors: Vaur
authors: Laboratoire de Biologie et Génétique du Cancer - Centre Normand de Génomique Médicale et Médecine Personnalisée, Centre François Baclesse, 3 avenue du général Harris, 14076, Caen Cedex 05, France. s.krieger@baclesse.fr.|Inserm U1079, Université de Médecine Pharmacie, Rouen, France. s.krieger@baclesse.fr.|UFR de Pharmacie, Université de Caen-Normandie, Caen, France. s.krieger@baclesse.fr.
authors: Sophie
authors: S
authors: Krieger
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D022981:Allelic Imbalance / Q000235:genetics*; D019313:BRCA1 Protein / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics; D016022:Case-Control Studies; D005260:Female; D019398:Genes, BRCA1; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D018095:Germ-Line Mutation / Q000235:genetics*; D061325:Hereditary Breast and Ovarian Cancer Syndrome / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D055815:Young Adult
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D014408:Biomarkers, Tumor
keywords: Allele specific expression; BRCA1; Breast; Cancer; Ovarian