6533b85afe1ef96bd12b8d46
RESEARCH PRODUCT
Comprehensive evaluation of coding region point mutations in microsatellite-unstable colorectal cancer
Riku KatainenLauri A. AaltonenXiaonan LiuEmmanouil T. DermitzakisEmmanouil T. DermitzakisOuti KilpivaaraAlexandra E. GylfeEevi KaasinenMinna TaipaleEsa PitkänenJussi TaipaleKristian OvaskaSari TuupanenLilli SaarinenHalit OngenHalit OngenHeikki RistolainenPia VahteristoKimmo PalinLaura Renkonen-sinisaloSelja KoskensaloUlrika A. HänninenJan BöhmAnna LepistöJiri HambergJohanna KondelinHeli RauanheimoJukka-pekka MecklinJukka-pekka MecklinNiko VälimäkiMikko P. TurunenTomas TanskanenSampsa HautaniemiKari SalokasAuli KarhuRoosa-maria PlakettiLeena YadavTatiana CajusoMarkku VarjosaloMervi Aavikkosubject
0301 basic medicineMedicine (General)Candidate geneclinical evaluationgenetic identificationgenetic analysisQH426-470medicine.disease_causeChromatin Epigenetics Genomics & Functional Genomicswhole exome sequencingddc:590mutator genesingle nucleotide polymorphismddc:576.5Gene Regulatory NetworksExomeExome sequencingCancercancer cellGeneticsMutation1184 Genetics developmental biology physiology3. Good healthgenetic codesyöpägeenitpriority journalMolecular Medicinewild typepoint mutationSystems MedicineColorectal Neoplasmscongenital hereditary and neonatal diseases and abnormalitiesddc:025.063/5703122 Cancerscancer geneticsSingle-nucleotide polymorphismcolorectal cancerBiologygene frequencyta3111mikrosatelliititcolony formationR105W geneArticle03 medical and health sciencesR5-920Gene interactionReportGeneticsmedicineHumanscontrolled studyhumanneoplasmspaksusuolisyöpäPoint mutationgene interactionhuman celltumor-related geneMicrosatellite instabilityMolecular Sequence AnnotationSequence Analysis DNAmedicine.diseaseta3122digestive system diseaseshuman tissueSTK38L gene030104 developmental biologyvalidation processgene expressionSMARCB1 genemicrosatellite instability3111 Biomedicinegene replicationReportsdescription
Microsatellite instability (MSI) leads to accumulation of an excessive number of mutations in the genome, mostly small insertions and deletions. MSI colorectal cancers (CRCs), however, also contain more point mutations than microsatellite-stable (MSS) tumors, yet they have not been as comprehensively studied. To identify candidate driver genes affected by point mutations in MSI CRC, we ranked genes based on mutation significance while correcting for replication timing and gene expression utilizing an algorithm, MutSigCV. Somatic point mutation data from the exome kit-targeted area from 24 exome-sequenced sporadic MSI CRCs and respective normals, and 12 whole-genome-sequenced sporadic MSI CRCs and respective normals were utilized. The top 73 genes were validated in 93 additional MSI CRCs. The MutSigCV ranking identified several well-established MSI CRC driver genes and provided additional evidence for previously proposed CRC candidate genes as well as shortlisted genes that have to our knowledge not been linked to CRC before. Two genes, SMARCB1 and STK38L, were also functionally scrutinized, providing evidence of a tumorigenic role, for SMARCB1 mutations in particular. © 2018 The Authors. Published under the terms of the CC BY 4.0 license Peer reviewed
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2018-09-01 |