Exome-Wide Somatic Microsatellite Variation Is Altered in Cells with DNA Repair Deficiencies

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dc.contributor.authorVaksman, Zalmanen
dc.contributor.authorFonville, Natalie C.en
dc.contributor.authorTae, Hongseoken
dc.contributor.authorGarner, Harold R.en
dc.date.accessioned2018-10-01T19:08:29Zen
dc.date.available2018-10-01T19:08:29Zen
dc.date.issued2014-11-17en
dc.description.abstractMicrosatellites (MST), tandem repeats of 1–6 nucleotide motifs, are mutational hot-spots with a bias for insertions and deletions (INDELs) rather than single nucleotide polymorphisms (SNPs). The majority of MST instability studies are limited to a small number of loci, the Bethesda markers, which are only informative for a subset of colorectal cancers. In this paper we evaluate non-haplotype alleles present within next-gen sequencing data to evaluate somatic MST variation (SMV) within DNA repair proficient and DNA repair defective cell lines. We confirm that alleles present within next-gen data that do not contribute to the haplotype can be reliably quantified and utilized to evaluate the SMV without requiring comparisons of matched samples. We observed that SMV patterns found in DNA repair proficient cell lines without DNA repair defects, MCF10A, HEK293 and PD20 RV:D2, had consistent patterns among samples. Further, we were able to confirm that changes in SMV patterns in cell lines lacking functional BRCA2, FANCD2 and mismatch repair were consistent with the different pathways perturbed. Using this new exome sequencing analysis approach we show that DNA instability can be identified in a sample and that patterns of instability vary depending on the impaired DNA repair mechanism, and that genes harboring minor alleles are strongly associated with cancer pathways. The MST Minor Allele Caller used for this study is available at https://github.com/zalmanv/MST_minor_allele_caller.en
dc.description.versionPublished versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1371/journal.pone.0110263en
dc.identifier.eissn1932-6203en
dc.identifier.issue11en
dc.identifier.othere110263en
dc.identifier.pmid25402475en
dc.identifier.urihttp://hdl.handle.net/10919/85202en
dc.identifier.volume9en
dc.language.isoenen
dc.publisherPLOSen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.titleExome-Wide Somatic Microsatellite Variation Is Altered in Cells with DNA Repair Deficienciesen
dc.title.serialPLOS ONEen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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