Large genomic deletions and duplications in the BRCA1 gene identified by a novel quantitative method

We applied a novel method to detect single or multiple exon deletions and amplifications in the BRCA1 gene. The test, called multiplex ligation-dependent probe amplification (MLPA), uses probes designed to hybridize adjacently to the target sequence. After ligation, the joined probes are amplified a...

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Bibliographic Details
Published in:	Cancer research (Chicago, Ill.) Vol. 63; no. 7; pp. 1449 - 1453
Main Authors:	HOGERVORST, Frans B. L, NEDERLOF, Petra M, KLUIJT, Irma, DOMMERING, Charlotte, VERHOEF, Senno, SCHOUTEN, Jan P, VAN'T VEER, Laura J, PALS, Gerard, GILLE, Johan J. P, MCELGUNN, Cathal J, GRIPPELING, Maartje, PRUNTEL, Roelof, REGNERUS, Rein, VAN WELSEM, Tibor, VAN SPAENDONK, Resie, MENKO, Fred H
Format:	Journal Article
Language:	English
Published:	Philadelphia, PA American Association for Cancer Research 01-04-2003
Subjects:	Biological and medical sciences Blotting, Southern Breast Neoplasms - genetics DNA Mutational Analysis - methods Exons Female Female genital diseases Gene Deletion Genes, BRCA1 Genetic Predisposition to Disease Gynecology. Andrology. Obstetrics Humans Mammary gland diseases Medical sciences Ovarian Neoplasms - genetics Polymerase Chain Reaction - methods Tumors Human Nucleotide sequence Family study Malignant tumor Female genital diseases Mammary gland diseases Ovarian diseases Ovary Gene amplification Investigation method Predisposition Deletion Molecular epidemiology Familial cancer Female Gene duplication Mammary gland Mutation Genome Quantitative analysis Tumor suppressor gene
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Summary:	We applied a novel method to detect single or multiple exon deletions and amplifications in the BRCA1 gene. The test, called multiplex ligation-dependent probe amplification (MLPA), uses probes designed to hybridize adjacently to the target sequence. After ligation, the joined probes are amplified and quantified. Our two diagnostic laboratories have tested in the recent years 805 families by conventional PCR-based techniques, and found 116 BRCA1 and 28 BRCA2 mutation-positive families. Using MLPA, we have tested the remaining 661 noninformative breast cancer families and identified five distinct BRCA1 germ-line mutations in five families: a deletion of exon 8, a deletion of exons 20-22, a duplication of exon 13 and exons 21-23, respectively, and a triplication, encompassing exons 17-19. Genomic deletions of BRCA1 constitute a substantial fraction of mutations in Dutch breast cancer families. If MLPA had been included in our initial BRCA1 testing, 33 families with a deletion or duplication would have been identified, representing 27% of the total 121 BRCA1 mutation-positive families. The MLPA test for BRCA1 ensures a sensitive and comprehensive high-throughput screening test for genomic rearrangement and can easily be implemented in the molecular analysis of BRCA1.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2
ISSN:	0008-5472 1538-7445