Screening for large rearrangements of the BRCA1 gene in German breast or ovarian cancer families using semi-quantitative multiplex PCR method.
Since the identification of the breast and ovarian cancer susceptibility genes BRCA1 and BRCA2, a large number of different germline mutations in both genes have been found by conventional PCR-based mutation detection methods. Complex germline rearrangements such as those reported in the BRCA1 gene are often not detectable by these standard diagnostic techniques. To detect large deletions or duplications encompassing one or more exons of the BRCA1 gene and in order to estimate the frequency of BRCA1 rearrangements in German breast or ovarian cancer families, a semi-quantitative multiplex PCR method was developed and applied to DNA samples of patients from families negatively tested for disease causing mutations in the BRCA1 and BRCA2 coding regions by direct sequencing. Out of 59 families analysed, one family was found to carry a rearrangement in the BRCA1 gene (duplication of exon 13). The results indicate that the semi-quantitative multiplex PCR method is useful for the detection of large rearrangements in the BRCA1 gene and therefore represents an additional valuable tool for mutation analysis of BRCA1 and BRCA2.
Hofmann
Wera
W
Department of Tumor Genetics, Max Delbrück Center for Molecular Medicine, Berlin, Germany. whofmann@mdc-berlin.de
Görgens
Heike
H
John
Anika
A
Horn
Denise
D
Hüttner
Christine
C
Arnold
Norbert
N
Scherneck
Siegfried
S
Schackert
Hans K
HK
D000328:Adult; D019313:BRCA1 Protein / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics*; D004273:DNA, Neoplasm / Q000097:blood / Q000235:genetics; D005190:Family; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D015321:Gene Rearrangement / Q000235:genetics*; D019398:Genes, BRCA1; D005820:Genetic Testing / Q000379:methods*; D005858:Germany / Q000453:epidemiology; D006801:Humans; D008214:Lymphocytes / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000235:genetics*; D016133:Polymerase Chain Reaction / Q000379:methods*; D012680:Sensitivity and Specificity
D019313:BRCA1 Protein; D004273:DNA, Neoplasm