title: Y179C, F486L and N550H are BRCA1 variants that may be associated with breast cancer in a Sicilian family: results of a 5-year GOIM (Gruppo Oncologico dell'Italia Meridionale) prospective study.
abstract: BACKGROUND
  Over 600 different pathogenic mutations have been identified in the BRCA1 gene. Nevertheless, numerous missense mutations of unknown biological function still exist. Understanding of biological significance of these mutations should help in genetic counselling to carriers and their families.
  
  
  METHODS
  A total of 104 patients with breast and/or ovarian cancer whose genetic counselling answered the criteria of the American Society of Clinical Oncology (ASCO 2003), were prospectively screened for mutations in all coding exons of the BRCA1 gene by automatic direct sequencing.
  
  
  RESULTS
  During these mutational screening procedures one case presented three mutations classified in the Breast Cancer Information Core Database as unknown variants. These were 655A/G found in exon 8 of BRCA1, 1575T/C and 1767A/C found in exon 11 of the same gene. The identification of the three unknown variants in the proband (16SIRIO) and in her mother and sister indicates that such alterations exist in cis.
  
  
  CONCLUSIONS
  Our results suggest that the charge and stechiometry variations determined by the changes in the amino acids Y179C, F486L and N550H might produce an effect on the conformation of the protein and, consequently, on its function.
authors.affiliation: Section of Medical Oncology and Section of Surgical Oncology, Department of Surgical and Oncology, Università di Palermo, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Augello
authors.forename: L
authors.initials: L
authors.lastname: Bruno
authors.forename: V
authors.initials: V
authors.lastname: Bazan
authors.forename: V
authors.initials: V
authors.lastname: Calò
authors.forename: V
authors.initials: V
authors.lastname: Agnese
authors.forename: S
authors.initials: S
authors.lastname: Corsale
authors.forename: S
authors.initials: S
authors.lastname: Cascio
authors.forename: G
authors.initials: G
authors.lastname: Gargano
authors.forename: M
authors.initials: M
authors.lastname: Terrasi
authors.forename: F
authors.initials: F
authors.lastname: Barbera
authors.forename: S
authors.initials: S
authors.lastname: Fricano
authors.forename: B
authors.initials: B
authors.lastname: Adamo
authors.forename: M R
authors.initials: MR
authors.lastname: Valerio
authors.forename: G
authors.initials: G
authors.lastname: Colucci
authors.forename: E
authors.initials: E
authors.lastname: Sumarcz
authors.forename: A
authors.initials: A
authors.lastname: Russo
mesh_terms: D000328:Adult; D019313:BRCA1 Protein / Q000737:chemistry / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics; D005091:Exons; D005192:Family Health; D005260:Female; D019398:Genes, BRCA1; D005817:Genetic Counseling; D014644:Genetic Variation; D018095:Germ-Line Mutation; D006801:Humans; D020125:Mutation, Missense; D010051:Ovarian Neoplasms / Q000235:genetics; D010375:Pedigree; D011446:Prospective Studies; D011487:Protein Conformation; D012802:Sicily
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D004273:DNA, Neoplasm