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DNA array-based method for detection of large rearrangements in the BRCA1 gene
Andrey Frolov1, Amanda H Prowse, Lisa Vanderveer
1Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA.
Genes, Chromosomes & Cancer
|September 28, 2002
Summary
Large gene rearrangements in BRCA1 are implicated in ovarian cancer, even when coding mutations are absent. A new DNA microarray assay detects these deletions, finding a novel 3-kb deletion in one ovarian tumor sample.
Area of Science:
- Genetics
- Oncology
- Molecular Biology
Background:
- Germline BRCA1/BRCA2 alterations are common in hereditary breast and ovarian cancers.
- Somatic mutations in BRCA1/BRCA2 are rare in sporadic tumors, despite frequent loss of heterozygosity.
- Current mutation detection assays often miss large gene rearrangements.
Purpose of the Study:
- To develop a fluorescence DNA microarray assay for detecting large gene rearrangements in BRCA1.
- To screen malignant ovarian tumors for such rearrangements.
Main Methods:
- Development of a fluorescence DNA microarray assay to screen for large gene rearrangements.
- Screening of 15 malignant ovarian tumor samples.
Main Results:
- One ovarian tumor sample exhibited a novel 3-kb deletion encompassing exon 17 of BRCA1.
- This deletion resulted in a frameshift mutation and was not present in the constitutive DNA.
- The deletion was not detectable by standard mutation detection assays.
Conclusions:
- Large gene rearrangements in BRCA1 should be considered in ovarian cancer mutational analysis.
- The developed microarray assay can efficiently screen for genomic rearrangements in cancer-associated genes.
- Somatic large gene rearrangements may play a role in sporadic ovarian cancers where point mutations are not found.