POLE F367S
Gene Variant Detail

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Gene POLE
Variant F367S
Impact List missense
Protein Effect loss of function
Gene Variant Descriptions POLE F367S lies within the exonuclease domain of the Pole protein (PMID: 29352080). F367S results in reduced exonuclease activity and increased replication error rates compared to wild-type Pole in in vitro assays (PMID: 29352080, PMID: 25228659).
Associated Drug Resistance
Category Variants Paths

POLE mutant POLE inact mut POLE F367S

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Transcript NM_006231.4
gDNA chr12:g.132675741A>G
cDNA c.1100T>C
Protein p.F367S
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
XM_011534795.3 chr12:g.132675741A>G c.1100T>C p.F367S RefSeq GRCh38/hg38
XM_011534799.2 chr12:g.132675741A>G c.1100T>C p.F367S RefSeq GRCh38/hg38
XM_047429018.1 chr12:g.132675741A>G c.1100T>C p.F367S RefSeq GRCh38/hg38
XM_011534795.4 chr12:g.132675741A>G c.1100T>C p.F367S RefSeq GRCh38/hg38
NM_006231.4 chr12:g.132675741A>G c.1100T>C p.F367S RefSeq GRCh38/hg38
XM_011534799.3 chr12:g.132675741A>G c.1100T>C p.F367S RefSeq GRCh38/hg38
XM_011534800 chr12:g.132675741A>G c.1100T>C p.F367S RefSeq GRCh38/hg38
NM_006231 chr12:g.132675741A>G c.1100T>C p.F367S RefSeq GRCh38/hg38
XM_011534795 chr12:g.132675741A>G c.1100T>C p.F367S RefSeq GRCh38/hg38
XM_011534799 chr12:g.132675741A>G c.1100T>C p.F367S RefSeq GRCh38/hg38
NM_006231.3 chr12:g.132675741A>G c.1100T>C p.F367S RefSeq GRCh38/hg38

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
POLE inact mut Advanced Solid Tumor predicted - sensitive Nivolumab Case Reports/Case Series Actionable In a Phase II trial, Opdivo (nivolumab) resulted in an objective response rate (ORR) of 38% (7/19; all partial responses) and a disease control rate (DCR) of 58% (11/19) at 12 weeks in patients with advanced solid tumors harboring a POLE mutation, and among assessable patients with an inactivating POLE mutation, along with high tumor mutational burden, treatment resulted in an ORR of 46% (5/11) and a DCR of 73% (8/11) (PMID: 35398880; NCT03012581). 35398880
POLE inact mut colorectal cancer predicted - sensitive unspecified immune checkpoint inhibitor Clinical Study - Cohort Actionable In a clinical study, immunotherapy resulted in improved clinical benefit in patients with metastatic colorectal cancer harboring POLE inactivating mutations (n=7, 3 complete responses, 3 partial responses, 1 stable disease (SD)) and durable response (remained on therapy with median follow up of 36 months) compared to microsatellite stable (MSS) patients harboring non-loss-of-function POLE mutations (n=7, 2 SD; median progression-free survival 3.6 months, p<0.0003) (Ann Oncol (2023) 34 (suppl_2): S448-S449). detail...
POLE inact mut colorectal carcinoma not applicable N/A Guideline Risk Factor Germline POLE inactivating mutations result in polymerase proofreading-associated polyposis and are associated with increased risk of developing colorectal carcinoma (NCCN.org). detail...
POLE inact mut colorectal cancer not applicable N/A Guideline Prognostic POLE inactivating mutations are associated with a more favorable prognosis in patients with colorectal cancer (NCCN.org). detail...
POLE inact mut Advanced Solid Tumor predicted - sensitive unspecified immune checkpoint inhibitor Clinical Study - Cohort Actionable In a retrospective analysis, treatment with immune checkpoint inhibitors including PD1/PD-L1 inhibitor monotherapies or in combination with CTLA inhibitors resulted in improved clinical benefit rate (82.4% vs 30.0%, p=0.013), median progression-free survival (15.1 vs 2.2 mo, p<0.001), overall survival (29.5 vs 6.8 mo, p<0.001), and treatment duration (15.5 vs 2.5 mo, p<0.001) in advanced solid tumor patients harboring pathogenic POLE mutations compared to those harboring benign mutations (PMID: 35108036). 35108036
POLE mutant Advanced Solid Tumor predicted - sensitive unspecified PD-L1 antibody Clinical Study - Cohort Actionable In a clinical study, immune checkpoint inhibitor (ICI) treatment, including CTLA4, PD-1, and PD-L1-targeting antibodies, resulted in prolonged overall survival (34 vs 18 months, p=0.004) in patients with advanced solid tumors harboring POLE or POLD1 mutations compared to wild-type patients, and POLE/POLD1 mutation served as a predictor of response to ICI (p=0.047, HR=1.41) independent of MSI-H status (PMID: 31415061). 31415061
POLE mutant Advanced Solid Tumor predicted - sensitive unspecified PD-1 antibody Clinical Study - Cohort Actionable In a clinical study, immune checkpoint inhibitor (ICI) treatment, including CTLA4, PD-1, and PD-L1-targeting antibodies, resulted in prolonged overall survival (34 vs 18 months, p=0.004) in patients with advanced solid tumors harboring POLE or POLD1 mutations compared to wild-type patients, and POLE/POLD1 mutation served as a predictor of response to ICI (p=0.047, HR=1.41) independent of MSI-H status (PMID: 31415061). 31415061
POLE mutant Advanced Solid Tumor predicted - sensitive unspecified CTLA4 antibody Clinical Study - Cohort Actionable In a clinical study, immune checkpoint inhibitor (ICI) treatment, including CTLA4, PD-1, and PD-L1-targeting antibodies, resulted in prolonged overall survival (34 vs 18 months, p=0.004) in patients with advanced solid tumors harboring POLE or POLD1 mutations compared to wild-type patients, and POLE/POLD1 mutation served as a predictor of response to ICI (p=0.047, HR=1.41) independent of MSI-H status (PMID: 31415061). 31415061