title: A mutation analysis of the BRCA1 gene in 140 families from southeast France with a history of breast and/or ovarian cancer.
abstract: A mutation analysis of the BRCA1 gene in 140 French families with a history of breast cancer or breast-ovarian cancer revealed several deleterious germline mutations, as well as rare sequence variants. The 19 genetics variants were of 15 different types, two of which had not been reported in the Breast cancer Information Core (BIC) database. Five distinct truncating mutations, leading to putative nonfunctional proteins, were identified out of 140 index cases (3.5%). One novel nonsense mutation, C4491T, was reported, whereas the four other BRCA1 deleterious mutations identified consisted of frequent frameshifts in the nucleotide sequence. One splice variant (331+3A>G) and thirteen missense variations leading to amino acid substitutions of unknown structural and functional importance were identified. Among these, two BRCA1 missense mutations, A120G and T243C could be considered as suspected deleterious. The first missense mutation modified the initiation codon (M1V) and the second (C39R) may have consequences on the structure and functioning of the BRCA1 protein by modifying cysteine ligands from the RING finger domain. As expected BRCA1 gene alteration, including missense mutations of unknown biological significance, were more frequent in families with a history of breast-ovarian-cancer (32%) than in breast-cancer-only families (12%).
authors.affiliation: Oncogenetic Laboratory, Centre Antoine Lacassagne, 33 avenue de Valombrose, 06189, Nice, France. philippe.rostagno@free.fr
authors.forename: Philippe
authors.initials: P
authors.lastname: Rostagno
authors.forename: Jeanine
authors.initials: J
authors.lastname: Gioanni
authors.forename: Eliane
authors.initials: E
authors.lastname: Garino
authors.forename: Pierre
authors.initials: P
authors.lastname: Vallino
authors.forename: Moise
authors.initials: M
authors.lastname: Namer
authors.forename: Marc
authors.initials: M
authors.lastname: Frenay
mesh_terms: D000328:Adult; D017398:Alternative Splicing; D019313:BRCA1 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics*; D003062:Codon; D018389:Codon, Nonsense; D004252:DNA Mutational Analysis; D019992:Databases as Topic; D005091:Exons; D005192:Family Health; D005260:Female; D016368:Frameshift Mutation; D005602:France; D006801:Humans; D008024:Ligands; D020125:Mutation, Missense; D010051:Ovarian Neoplasms / Q000235:genetics*; D010375:Pedigree; D012307:Risk Factors
chemical_list: D019313:BRCA1 Protein; D003062:Codon; D018389:Codon, Nonsense; D008024:Ligands