POLE mutation

To add to this excellent thread, not all POLE mutations = high #TMB as you may notice on #NGS report - most pathogenic #POLE mutations that lead to ultra-mutated #crcsm #MSS phenotype cluster around the active DNA-binding sites of the exonuclease proofreading domain (@jgong15)

Dr. Starr on the Characterization of POLE/POLD1 Mutations in Colorectal Adenocarcinoma https://t.co/oIK9OWCxKB via @onclive (@NANETS1)

More adjuvant treatment decisions are being driven by molecular profiling for patients with endometrial cancer with POLE mutations, MMR status, and other genetic alterations dictating the best course of therapy. @RSalaniMD @UCLAJCCC #gynsm https://t.co/EXcScfYXT3 (@OncLive)

I know of a #CRC patient with POLE mutation (TMB over 300) doing well on pembro (@manjuggm)

#TumorBoardTuesday 💥Wow, we dove🤿 deep into the science🔬this week‼️ THANK YOU to @drjasonstarr & @TuckerCoston for leading us through a🗣️on POLE mutations in #colorectalcancer 👉Don’t forget your🆓#CME credit Answer 2 quick❓ Here's the postest🔗 https://t.co/jUZeIb8exo (@TumorBoardTues)

#TumorBoardTuesday Before Tuesday's🗣️ 🧠Log in⌨️& earn🥇your🆓CME Credits‼️ ✅2 Pre-case❓on POLE mutations, #ColorectalCancer & #PrecisionMedicine @CCAlliance CME info & Pretest: https://t.co/63osUKLysL ➡️Tell us from what point of view you are joining this🗣️❓ @MPishvaian (@TumorBoardTues)

Wang et al. show in #colorectalcancer patients that #NTRK-positive tumours have an increased tumour mutation burden, a higher MSI frequency, and an enrichment of POLE/POLD1 mutations compared to a molecularly unselected #CRC population. #ASCO21 @ASCO @MNagasaka @oncoOuLungCA (@ntrkconnectinfo)

At Esmo 2020 we presented the early results of Acse trial investigating nivolumab in progressive advanced POLE mutated patients and activity was observed in patients with metastatic CRC or endometrial cancers (@BenjcRousseau)

POLE mutated endometrial cancers are 1/4 TCGA molecular groups. In endometrial cancer associated with better prognosis despite higher risk features- better tx response or immune surveillance? May explain some cases of MMR loss because of hypermutated state. (@CaseCos)

Yes thats why i specially check if the NGS panel includes POLE mutations esp in Endometrial and GI cancers . Won't be surprised if it gets tissue agnostic approval for IO Rx (@oncologician)

Here are some important clinicopathological findings in patients with POLE mutated endometrial cancers from @LJTafeMD #cap20virtual (@DrSMBean)

Great. Would have done the same! These patients with pole mutations respond very well and usually have Uber high TMb-one of the areas where I think this biomarker is helpful in #crcsm (@DrR_DUNNE)

hello i have bowel cancer and pole mutation (@g5Skl4XtWgRZOYk)

Is this observation (lack of effect of the increase in TMB & expansion of neoantigens targeting lost HLA-alleles)specific to ICI response in NSCLC or is this widely applicable to other cancers such as CRC? What about increase in TMB due to POLE mutations? Role of HLA-LOH there? (@manjuggm)

There may be other subsets of #ColorectalCancer patients who benefit from #Immunotherapy as well, including those with POLE mutations. NGS in this population is critical-have seen amazing responses #ColorectalCancerAwarenessMonth https://t.co/kgHAVR2k6j (@DrR_DUNNE)

POLE mutations in CRC <50 years, esp P286R.6% or 10% prevalence.. Is this mutation added to genomic and liquid biopsy panels? @Natera_Oncology @GuardantHealth @freenome @GrailBio @agrothey @pashtoonkasi Copying @mending_stories @fireflyann (@manjuggm)

to your question about testing. @AdamGomezMD tweeted "@StanfordPath has developed standalone POLE mutation testing, also detected in colorectal adenocarcinoma with intact MMR, would otherwise be missed by routine screening for hypermutation " https://t.co/Qc1O8YZE52 (@fireflyann)

POLE mutation: (V411L) -- dramatic response to pembro and PD1 inh. BRAF mutant CRC: 10% of CRC. Mechanism of resistance? Combo therapy: BRAFi + MEKi + EGFRi (or doublet) showed some long term responses. (@TheBloodMD)