title: Germline mutations of TP53 and BRCA2 genes in breast cancer/sarcoma families.
abstract: The genetic aetiology of familial aggregations of breast cancer and sarcomas has been elucidated only in part. In this study, 23 unrelated individuals from families with one case of sarcoma and at least one case of breast cancer were screened for mutations in the TP53, BRCA1 and BRCA2 genes. Families were classified according to their conformity to the criteria defining the Li-Fraumeni syndrome (LFS), Li-Fraumeni-like (LFL) syndrome and hereditary breast/ovarian cancer (HBOC). Germline TP53 mutations were identified in three instances (13%), including one LFS and two LFL families, while none of the non-LFS/non-LFL families had a TP53 mutation. Three cases (13%), including one with a TP53 mutation, carried BRCA2 mutations. Of these, two were observed in LFL/HBOC families and the other one in a non-LFS/non-LFL/HBOC family, while none of the non-HBOC families tested positive. These findings suggest that the screening of BRCA2, in addition to TP53, may be appropriate for the molecular characterisation of breast cancer/sarcoma families, with practical implications for counselling and clinical management.
authors.affiliation: Medical Genetics Service, Department of Experimental Oncology and Laboratories, Istituto Nazionale Tumori, Milan, Italy.
authors.forename: Siranoush
authors.initials: S
authors.lastname: Manoukian
authors.forename: Bernard
authors.initials: B
authors.lastname: Peissel
authors.forename: Valeria
authors.initials: V
authors.lastname: Pensotti
authors.forename: Monica
authors.initials: M
authors.lastname: Barile
authors.forename: Laura
authors.initials: L
authors.lastname: Cortesi
authors.forename: Silvia
authors.initials: S
authors.lastname: Stacchiotti
authors.forename: Monica
authors.initials: M
authors.lastname: Terenziani
authors.forename: Floriana
authors.initials: F
authors.lastname: Barbera
authors.forename: Graziella
authors.initials: G
authors.lastname: Pasquini
authors.forename: Simona
authors.initials: S
authors.lastname: Frigerio
authors.forename: Marco A
authors.initials: MA
authors.lastname: Pierotti
authors.forename: Paolo
authors.initials: P
authors.lastname: Radice
authors.forename: Gabriella
authors.initials: G
authors.lastname: Della-Torre
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics*; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D016158:Genes, p53 / Q000235:genetics*; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D008297:Male; D020125:Mutation, Missense / Q000235:genetics; D010375:Pedigree; D016133:Polymerase Chain Reaction / Q000379:methods; D012509:Sarcoma / Q000235:genetics*