TY - JOUR
T1 - Novel BRCA1 mutations and more frequent intron-20 alteration found among 236 women from Western Poland
AU - Sobczak, Krzysztof
AU - Kozłowski, Piotr
AU - Napierała, Marek
AU - Czarny, Jakub
AU - Woźniak, Marcin
AU - Kapuscinska, Małgorzata
AU - Łośko, Małgorzata
AU - Koziczak, Magdalena
AU - Jasińska, Anna
AU - Powierska, Jolanta
AU - Braczkowski, Ryszard
AU - Brȩborowicz, Jan
AU - Godlewski, Dariusz
AU - Mackiewicz, Andrzej
AU - Krzyzosiak, Włodzimierz
N1 - Funding Information:
This work was supported by grant from State Committee for Scientific Research Nr 6 P207 106 06, by the Social Foundation ‘People for People’ and by donation from Banyu Tsukuba Research Institute in Collaboration with Merck Sharp & Dohme Research Laboratories, Banyu Pharmaceutical Co., Ltd., Tsukuba Techno-Park, Ohkubo 3, Tsukuba 300-33, Japan.
PY - 1997
Y1 - 1997
N2 - Three different novel BRCA1 mutations, five independent cases of the same 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 cancer, 80 controls and 34 unselected breast cancer tissue specimens. All mutations and variants were germline. The 4153 delA frameshift mutation, the Tyr105Cys missense mutation and two cases of the alteration in intron-20 were found in the group of healthy women with positive family history. Two other cases of the intronic insertion were found in unselected controls. Their carriers had no family history of breast or ovarian cancer but other cancers occurred in their families. The 1782 Trp/STOP nonsense mutation and one case of the insertion in Intron-20 were first found in tissue specimens of breast cancer patient and breast/ovarian cancer patient, respectively. Their carriers also had no family history of breast or ovarian cancer. The distribution of the insertion in intron-20 in analysed groups and results of RT-PCR experiments suggest a less prominent role for this variant considered earlier a splicing mutation. This study shows also, that more population-oriented research is needed, involving women with less profound or even no family history of breast and ovarian cancer, to better understand the role and significance of different BRCA1 variants and mutations.
AB - Three different novel BRCA1 mutations, five independent cases of the same 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 cancer, 80 controls and 34 unselected breast cancer tissue specimens. All mutations and variants were germline. The 4153 delA frameshift mutation, the Tyr105Cys missense mutation and two cases of the alteration in intron-20 were found in the group of healthy women with positive family history. Two other cases of the intronic insertion were found in unselected controls. Their carriers had no family history of breast or ovarian cancer but other cancers occurred in their families. The 1782 Trp/STOP nonsense mutation and one case of the insertion in Intron-20 were first found in tissue specimens of breast cancer patient and breast/ovarian cancer patient, respectively. Their carriers also had no family history of breast or ovarian cancer. The distribution of the insertion in intron-20 in analysed groups and results of RT-PCR experiments suggest a less prominent role for this variant considered earlier a splicing mutation. This study shows also, that more population-oriented research is needed, involving women with less profound or even no family history of breast and ovarian cancer, to better understand the role and significance of different BRCA1 variants and mutations.
KW - BRCA1
KW - Mutations and variants
KW - Polish women
KW - Positive family history
KW - SSCP-heteroduplex analysis
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U2 - 10.1038/sj.onc.1201360
DO - 10.1038/sj.onc.1201360
M3 - Article
C2 - 9362443
AN - SCOPUS:9844244554
SN - 0950-9232
VL - 15
SP - 1773
EP - 1779
JO - Oncogene
JF - Oncogene
IS - 15
ER -