Germline mutations at @entity5345 or @entity2674 genes result in susceptibility to @entity5344 . @entity5345 - and @entity2674 -associated @entity5 have distinct histologic and molecular phenotypes, as compared to sporadic @entity0 . Typically, a higher grade of @entity5 is observed in BRCA-associated @entity5 . A number of studies have suggested that @entity5345 and @entity2674 proteins are of importance in DNA repair and maintenance of genome integrity, bringing about molecular models of @entity5 pathogenesis. In particular, alterations at @entity876 gene have been suggested to be a necessary step in the tumorigenesis of @entity189 . In fact, BRCA-associated @entity0 have higher @entity876 mutation frequencies than sporadic ones. At present, very little is known regarding BRCA non-associated @entity5 (termed BRCAx @entity5 ). To our knowledge no data is available on @entity876 alterations in this sub-group of @entity5 . In this study @entity876 alteration frequencies were evaluated in 13 @entity5345 , 11 @entity2674 and 55 BRCAx @entity0 . @entity5 samples were analyzed for @entity876 gene mutations by PCR-SSCP/direct sequencing, and for @entity876 protein overexpression by immunohistochemistry (IHC). Altogether, @entity876 alterations were detected in 54% of @entity5345 @entity5 compared with 5% of BRCAx @entity5 . No @entity876 alteration was found in @entity2674 @entity5 . While loss of @entity876 checkpoint control is likely to be an important step in the molecular pathogenesis of @entity5345 -associated @entity5 , our data seem to indicate a @entity876 -independent molecular mechanism underlying BRCAx neoplastic transformation.

@entity876 inactivation is a rare event in @entity0 negative for XXXX and @entity2674 mutations.

@entity0 :: ('MESH:D001943', 'Disease') :: ['breast cancers', 'breast tumors'] @entity5344 :: ('MESH:D061325', 'Disease') :: ['breast and ovarian cancers'] @entity5345 :: ('672', 'Gene') :: ['BRCA1', 'BRCAI'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'cancers', 'Tumor', 'familial tumors', 'malignancy', 'tumors'] @entity2674 :: ('675', 'Gene') :: ['BRCA2'] @entity189 :: ('MESH:D002277', 'Disease') :: ['BRCA-associated carcinomas'] @entity876 :: ('7157', 'Gene') :: ['p53']
@entity5345 :: (672,Gene) :: ['BRCA1']
