Table 1 Characteristics of Polε mutations studied in this work
ClassificationHuman POLE VariantTumor TypesMutation OriginNo. Times ReportedaMMR Status of TumorsReferences
Exo domain, at DNA binding cleftD275VEC, GBM, LuCSomatic3MSSChurch et al. (2013), Campbell et al. (2017)
P286HCRC, GBMSomatic2MSSCancer Genome Atlas Network (2012), Campbell et al. (2017)
F367SCRC, ECSomatic5MSS&MSIYoshida et al. (2011), Cancer Genome Atlas Network (2012), Grossman et al. (2016), McConechy et al. (2016)
L424VCRC, EC, BrC, GBMSomatic5MSSCancer Genome Atlas Research Network (2013), Shinbrot et al. (2014), Stenzinger et al. (2014), Köbel et al. (2016), Andrianova et al. (2017)
CRC, EC, LC, DuC, OC, GBMGermline24MSSPalles et al. (2013), Valle et al. (2014), Chubb et al. (2015), Elsayed et al. (2015), Spier et al. (2015), Johanns et al. (2016)
P436REC, CRCSomatic7MSSCancer Genome Atlas Network (2012), Billingsley et al. (2015), Talhouk et al. (2015), Grossman et al. (2016), McConechy et al. (2016), Campbell et al. (2017)
S459FCRC, EC, HGG, AA, GBM, DuCSomatic27MSSCancer Genome Atlas Network (2012), Stenzinger et al. (2014), Erson-Omay et al. (2015), Shlien et al. (2015), Domingo et al. (2016), Giannakis et al. (2016), Grossman et al. (2016), Jansen et al. (2016), Wong et al. (2016), Campbell et al. (2017), Zehir et al. (2017)
Exo domain, distant from DNA binding cleftV411LEC, CRC, USC, GBM, OC, STAD, HGG, KC, PCSomatic122MSSCancer Genome Atlas Network (2012), Church et al. (2013, 2015), Cancer Genome Atlas Research Network (2013), Zhao et al. (2013), Meng et al. (2014), Shinbrot et al. (2014), Billingsley et al. (2015), Erson-Omay et al. (2015), Hoang et al. (2015), Talhouk et al. (2015), Domingo et al. (2016), Giannakis et al. (2016), Jansen et al. (2016), McConechy et al. (2016), Mehnert et al. (2016), Wong et al. (2016), Campbell et al. (2017), Espinosa et al. (2017), Gong et al. (2017), Zehir et al. (2017)
CRCGermline1MSSWimmer et al. (2017)
Outside Exo domain, MSI tumorsR231HCRCSomatic1MSICancer Genome Atlas Network (2012)
R762WCRCSomatic1MSICancer Genome Atlas Network (2012)
A966VCRCSomatic1MSISeshagiri et al. (2012)
Outside Exo domain, MSS tumorsF104LCRC, PXASomatic2MSSSeshagiri et al. (2012), Shlien et al. (2015)
D1752NCRCSomatic1MSSCancer Genome Atlas Network (2012)
SNPN336SGermlineNCBI SNP database
  • a Indicates the number of times the variant has been reported in whole-exome or targeted sequencing studies of all cancer types. Because many studies analyzed only selected exons of POLE, these numbers do not necessarily reflect the relative frequency of each variant.

  • AA, anaplastic astrocytoma; BrC, breast carcinoma; CRC, colorectal cancer; DuC, duodenal carcinoma; EC, endometrial cancer; GBM, glioblastoma; HGG, high grade glioma; KC, kidney cancer; LC, liver cancer; LuC, lung cancer; OC, ovarian cancer; PC, prostate cancer; PXA, pleomorphic xanthoastrocytoma; STAD, stomach adenocarcinoma; USC, uterine serous carcinoma.