Linked Life Data

18330910

Source:http://linkedlifedata.com/resource/pubmed/id/18330910

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2008-3-17
pubmed:abstractText
Disease-predisposing germline mutations in cancer susceptibility genes may consist of large genomic rearrangements that are challenging to detect and characterize using standard PCR-based mutation screening methods. Here, we describe a custom-made zoom-in microarray comparative genomic hybridization (CGH) platform of 60mer oligonucleotides. The 4 x 44 K array format provides high-resolution coverage (200-300 bp) of 400-700 kb genomic regions surrounding six cancer susceptibility genes. We evaluate its performance to accurately detect and precisely map earlier described or novel large germline deletions or duplications occurring in BRCA1 (n=11), BRCA2 (n=2), MSH2 (n=7), or MLH1 (n=9). Additionally, we demonstrate its applicability for uncovering complex somatic rearrangements, exemplified by zoom-in analysis of the PTEN and CDKN2A loci in breast cancer cells. The sizes of rearrangements ranged from several 100 kb, including large flanking regions, to <500-bp deletions, including parts of single exons that would be missed by standard multiplex ligation-dependent probe amplification (MLPA) methods. Zoom-in CGH arrays accurately defined the borders of rearrangements, allowing convenient design of primers for sequence determination of the breakpoints. The array platform can be streamlined for a particular application, e.g., focusing on breast cancer susceptibility genes, with increased capacity using multiformat design, and represents a valuable new tool and complement for genetic screening in clinical diagnostics.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1098-1004
pubmed:author
pubmed:copyrightInfo
Copyright 2008 Wiley-Liss, Inc.
pubmed:issnType
Electronic
pubmed:volume
29
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
555-64
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:18330910-Adaptor Proteins, Signal Transducing, pubmed-meshheading:18330910-Chromosome Mapping, pubmed-meshheading:18330910-Female, pubmed-meshheading:18330910-Gene Rearrangement, pubmed-meshheading:18330910-Genes, BRCA1, pubmed-meshheading:18330910-Genes, BRCA2, pubmed-meshheading:18330910-Genetic Counseling, pubmed-meshheading:18330910-Genetic Testing, pubmed-meshheading:18330910-Genomics, pubmed-meshheading:18330910-Germ-Line Mutation, pubmed-meshheading:18330910-Humans, pubmed-meshheading:18330910-Male, pubmed-meshheading:18330910-MutS Homolog 2 Protein, pubmed-meshheading:18330910-Nuclear Proteins, pubmed-meshheading:18330910-Nucleic Acid Hybridization, pubmed-meshheading:18330910-Oligonucleotide Array Sequence Analysis, pubmed-meshheading:18330910-Sequence Deletion
pubmed:year
2008
pubmed:articleTitle
Detection and precise mapping of germline rearrangements in BRCA1, BRCA2, MSH2, and MLH1 using zoom-in array comparative genomic hybridization (aCGH).
pubmed:affiliation
Division of Oncology, Department of Clinical Sciences, Lund University, Lund, Sweden.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't