Somatic intronic microsatellite loci differentiate glioblastoma from lower-grade gliomas

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dc.contributor.authorKarunasena, Enushaen
dc.contributor.authorMcIver, Lauren J.en
dc.contributor.authorRood, Brian R.en
dc.contributor.authorWu, Xiaoweien
dc.contributor.authorZhu, Hongxiaoen
dc.contributor.authorBavarva, Jasmin H.en
dc.contributor.authorGarner, Harold R.en
dc.contributor.departmentStatisticsen
dc.contributor.departmentFralin Life Sciences Instituteen
dc.date.accessioned2017-01-29T02:15:43Zen
dc.date.available2017-01-29T02:15:43Zen
dc.date.issued2014-08-15en
dc.description.abstractGenomic studies of glioma sub-types have amassed new disease specific mutations, yet these only partially explain how mutations are linked to predisposition or progression. We hypothesized that microsatellite variation could expand the understanding of glioma etiology. Furthermore, germline markers for gliomas are typically undetectable; therefore, we also hypothesize that the predictability of cancer-associated microsatellite loci in germline DNA may support the current hypothesis of a glioma cell of origin. In this study, “normal” germline exome sequenced DNA from the 1000 Genomes Project (n=390) were compared with exome sequences from germlines of subjects with WHO grade II and III lower-grade glioma (LGG, n=136) and WHO grade IV glioblastoma (GBM, n=252) from The Cancer Genome Atlas to identify microsatellite loci non-randomly associated with glioma. From germline data, we identified 48 GBM-specific loci, 42 Lower-grade glioma specific loci and 29 loci that distinguish GBM from LGG (p≤ 0.01). We then attempted to distinguish WHO grade II glioma (n=67) from GBM resulting in 8 informative loci. Significantly, in all glioma grades, comparisons between tumor and matched germline sequences demonstrated no significant differences in these variants (p≥ 0.01). Therefore, these microsatellite loci are considered to be components of grade-specific signatures for glioma which distinguish germline sequences of individuals with cancer from those of individuals that are “normal”. In order to better understand the significance of these loci, we identified biological processes enriched in genes with these variants. Most strikingly, six helicase genes were enriched in the GBM cohort (p≤ 1.0 x10<sup>-3</sup>). The preservation of these glioma-specific loci could therefore serve as valuable diagnostic and therapeutic markers; especially since the heterogeneity of tumor cell populations can obscure the identification of mutations preceding a metastatic phenotype.en
dc.description.versionPublished versionen
dc.format.extent6003 - 6014 (12) page(s)en
dc.identifier.issn1949-2553en
dc.identifier.issue15en
dc.identifier.urihttp://hdl.handle.net/10919/74447en
dc.identifier.volume5en
dc.language.isoenen
dc.publisherImpact Journalsen
dc.relation.urihttp://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000347919500013&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=930d57c9ac61a043676db62af60056c1en
dc.rightsCreative Commons Attribution 3.0 Unporteden
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/en
dc.subjectOncologyen
dc.subjectCell Biologyen
dc.subjectGBMen
dc.subjectmicrosatelliteen
dc.subjectgliomaen
dc.subjectoligodendrogliomaen
dc.subjecthelicaseen
dc.subjectubiquitin proteasome systemen
dc.subjectRNA-SEQen
dc.subjectREVEALSen
dc.subjectCANCERen
dc.subjectSEQUENCESen
dc.subjectREPEATSen
dc.subjectORIGINen
dc.subjectCELLen
dc.subjectINFLAMMATIONen
dc.subjectINSTABILITYen
dc.subjectEUKARYOTESen
dc.titleSomatic intronic microsatellite loci differentiate glioblastoma from lower-grade gliomasen
dc.title.serialONCOTARGETen
dc.typeArticle - Refereeden
pubs.organisational-group/Virginia Techen
pubs.organisational-group/Virginia Tech/All T&R Facultyen
pubs.organisational-group/Virginia Tech/Faculty of Health Sciencesen
pubs.organisational-group/Virginia Tech/Scienceen
pubs.organisational-group/Virginia Tech/Science/COS T&R Facultyen
pubs.organisational-group/Virginia Tech/Science/Statisticsen
pubs.organisational-group/Virginia Tech/University Research Institutesen

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