Comprehensive analysis of 989 patients with breast or ovarian cancer provides BRCA1 and BRCA2 mutation profiles and frequencies for the German population. Meindl, A. Int J Cancer, 97(4):472-80., 2002.
abstract   bibtex   
The main focus of this German-wide multi-center study was to establish a BRCA1/2 mutation profile and to determine family types with high frequencies of mutations in these genes. In a comprehensive study, the entire coding sequences of the breast cancer genes BRCA1 and BRCA2 were analyzed in 989 unrelated patients from German breast/ovarian cancer families. A total of 77 BRCA1 and 63 BRCA2 distinct deleterious mutations were found in 302 patients. More than (1/3) of these mutations are novel and might be specific for the German population. Eighteen common mutations were found in 68% of cases in BRCA1 and 13 recurrent mutations in 44% of cases in BRCA2, facilitating prescreening approaches. Haplotype analysis indicate that 14 out of 20 recurrent mutations are likely originating from a common founder. An additional 50 different rare sequence variants with unknown relevance for tumorigenesis were found in 72 families. Correlation of BRCA1/BRCA2 detection rates with family history identified families with both breast and ovarian cancer to be at highest risk for BRCA1/BRCA2 mutations (43% and 10%, respectively), followed by families with at least 2 premenopausal cases of breast cancer (24% BRCA1 and 13% BRCA2 mutations). These data provide strong evidence for further predisposing genes in the German population. In breast cancer families with 2 or 3 affected females but only a single or no premenopausal case, mutations were detected with low frequencies (about 10% or less for both genes). The decision for or against molecular diagnosis is now aided by considering the expected mutation detection rates that greatly depend on family history and structure.
@article{
 title = {Comprehensive analysis of 989 patients with breast or ovarian cancer provides BRCA1 and BRCA2 mutation profiles and frequencies for the German population},
 type = {article},
 year = {2002},
 identifiers = {[object Object]},
 keywords = {*Genes, BRCA1,*Genes, BRCA2,*Mutation,Adult,Age of Onset,Alleles,Breast Neoplasms/epidemiology/*genetics,Comparative Study,DNA Mutational Analysis,DNA, Neoplasm/genetics,Exons/genetics,Female,Founder Effect,Frameshift Mutation,Gene Frequency,Genetic Predisposition to Disease,Genetic Screening,Germany/epidemiology,Haplotypes/genetics,Human,Male,Middle Age,Mutation, Missense,Neoplasms, Multiple Primary/epidemiology/genetics,Neoplastic Syndromes, Hereditary/epidemiology/*gen,Ovarian Neoplasms/epidemiology/genetics,Prevalence,RNA Splicing/genetics,Risk Factors,Sequence Deletion,Support, Non-U.S. Gov't},
 pages = {472-80.},
 volume = {97},
 id = {8ed5a985-2a75-32ed-8427-3fb16b9ce255},
 created = {2017-06-19T13:42:58.702Z},
 file_attached = {false},
 profile_id = {de68dde1-2ff3-3a4e-a214-ef424d0c7646},
 group_id = {b2078731-0913-33b9-8902-a53629a24e83},
 last_modified = {2017-06-19T13:42:58.818Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {true},
 hidden = {false},
 source_type = {Journal Article},
 notes = {<m:note>eng<m:linebreak/>Journal Article<m:linebreak/>Multicenter Study</m:note>},
 abstract = {The main focus of this German-wide multi-center study was to establish a BRCA1/2 mutation profile and to determine family types with high frequencies of mutations in these genes. In a comprehensive study, the entire coding sequences of the breast cancer genes BRCA1 and BRCA2 were analyzed in 989 unrelated patients from German breast/ovarian cancer families. A total of 77 BRCA1 and 63 BRCA2 distinct deleterious mutations were found in 302 patients. More than (1/3) of these mutations are novel and might be specific for the German population. Eighteen common mutations were found in 68% of cases in BRCA1 and 13 recurrent mutations in 44% of cases in BRCA2, facilitating prescreening approaches. Haplotype analysis indicate that 14 out of 20 recurrent mutations are likely originating from a common founder. An additional 50 different rare sequence variants with unknown relevance for tumorigenesis were found in 72 families. Correlation of BRCA1/BRCA2 detection rates with family history identified families with both breast and ovarian cancer to be at highest risk for BRCA1/BRCA2 mutations (43% and 10%, respectively), followed by families with at least 2 premenopausal cases of breast cancer (24% BRCA1 and 13% BRCA2 mutations). These data provide strong evidence for further predisposing genes in the German population. In breast cancer families with 2 or 3 affected females but only a single or no premenopausal case, mutations were detected with low frequencies (about 10% or less for both genes). The decision for or against molecular diagnosis is now aided by considering the expected mutation detection rates that greatly depend on family history and structure.},
 bibtype = {article},
 author = {Meindl, A},
 journal = {Int J Cancer},
 number = {4}
}

Downloads: 0