NOVEL BRCA1 MUTATIONS AND MORE FREQUENT INTRON-20 ALTERATION FOUND AMONG 236 WOMEN FROM WESTERN POLAND

Three different novel BRCA1 mutations, five independent cases of the s ame 12 bp insertion-duplication in intron-20 and two novel rare BRCA1 sequence variants were identified among 122 Polish women with positive , in most cases moderate family history of breast and/or ovarian cance r, 80 controls and 34 unselected breast cancer tissue specimens, All m utations and variants were germline. The 4153 delA frameshift mutation , the Tyr105Cys missense mutation and two cases of the alteration in i ntron-20 were found in the group of healthy women with positive family history. Two other cases of the intronic insertion mere found in unse lected controls. Their carriers had no family history of breast or ova rian cancer but other cancers occurred in their families. The 1782 Trp /STOP nonsense mutation and one case of the insertion in intron-20 wer e first found in tissue specimens of breast cancer patient and breast/ ovarian cancer patient, respectively. Their carriers also had no famil y history of breast or ovarian cancer. The distribution of the inserti on in intron-20 in analysed groups and results of RT-PCR experiments s uggest a less prominent role for this variant considered earlier a spl icing mutation. This study shows also, that more population-oriented r esearch is needed, involving women with less profound or even no famil y history of breast and ovarian cancer, to better understand the role and significance of different BRCA1 variants and mutations.