MUTATION IN BRIEF HUMAN MUTATION Mutation in Brief #635 (2003) Online © 2003 WILEY-LISS, INC. DOI: 10.1002/humu.9164 Received 16 December 2002; accepted revised manuscript 14 April 2003. BRCA1 and BRCA2 Mutations in Breast/Ovarian Cancer Patients from Central Italy L. Stuppia 1,2 , P. Di Fulvio 1 , G. Aceto 3 , S. Pintor 1 , S. Veschi 3 , V. Gatta 1 , A. Colosimo 1 , E. Cianchetti 4 , A. Cama 3 , R. Mariani-Costantini 3 , P. Battista 3 , and G. Palka 1,5* Dipartimenti di 1 Scienze Biomediche e di 3 Oncologia e Neuroscienze, Università “G. D’Annunzio”, Chieti; 2 Istituto di Citomorfologia Normale e Patologica C.N.R., Chieti; 4 Chirurgia Generale, Ospedale Civile di Ortona; 5 Servizio di Genetica Umana, Ospedale Civile di Pescara, Italy *Correspondence to: Giandomenico Palka, M.D., Dipartimento di Scienze Biomediche, Sezione di Genetica Medica, Università “G. D’Annunzio”, Via dei Vestini 35, 66013 Chieti, Italy; Tel.: (+39) 0871 3554137; Fax: (+39) 0871 3554135; E-mail: gdpalka@unich.it Communicated by Mark H. Paalman We report on the screening of the entire BRCA1/BRCA2 coding sequence by SSCP, PTT, and direct sequencing in 68 Italian families with recurrent breast or ovarian cancer. For each investigated proband, the probability of being carrier of a BRCA1/BRCA2 mutation was evaluated using the BRCAPRO software. We detected BRCA1/BRCA2 mutations in 8 patients (11.7%). However, if considering only patients with a carrier probability >10%, the detection rate was 36.8%, confirming the usefulness of the BRCAPRO software. One change (BRCA1 4172insT) was a novel mutation not reported in BIC database. © 2003 Wiley- Liss, Inc. KEY WORDS: cancer, breast cancer, ovarian cancer, BRCA1, BRCA2, BRCAPRO software INTRODUCTION Breast Cancer (BC) is the most common malignancy in women in the western world (Parkin, 1998). Hereditary BC accounts for 5-10% of all cases and is characterised by dominant inheritance, early onset, severe course of the disease, bilaterality and frequent association with ovarian cancer (OC) (Claus et al., 1996). Linkage analysis in large kindreds with hereditary BC lead to the identification of two genes, BRCA1 (17q21, MIM* 113705) and BRCA2 (13q14, MIM* 600185), whose mutations induce a 5-fold elevated lifetime risk of BC and OC (Miki et al., 1994; Wooster et al., 1995; Struewing et a., 1997). The prevalence of BRCA1/BRCA2 mutations in families with BC and OC varies widely among populations, with some ethnic groups presenting a small number of common mutations, likely due to a “founder effect”, and others showing several unique mutations (Szabo and King, 1997). However, the majority of studies carried out in many world countries indicates that the prevalence of BRCA1/BRCA2 mutations is lower than that originally suggested by early studies on large families with several affected members (Ford et al., 1998; Malone et al., 1998; Osorio et al., 2000; Konstantopoulou et al., 2000; Llort et al., 2002; Tereschenko et al., 2002). Studies performed in Italy reported different prevalences of BRCA1/BRCA2 mutations, likely due to the different selection criteria and to the variability of the employed techniques (Caligo et al., 1996; De Benedetti et al., 1996; Montagna et al., 1996; De Benedetti et al., 1998; Santarosa et al., 1998; Santarosa et al., 1999; Ottini et al., 2000; Baudi et al., 2001).