QPCR POLE Mutation Analysis Kit

Features

• Low DNA input - 8 ng/sample (2 x 4 ng)
• Fast results – 1.5 h from DNA to result
• No additional bioinformatics - Intuitive data analysis using instrument software, no further calculation required
• Use your standard qPCR instrument

The QPCR POLE Mutation Analysis Kit detects 6 different base substitutions and can distinguish 5 mutations. These comply with the relevant clinical guidelines (ESMO) [1] for risk classification of endometrial cancer. The QPCR POLE Mutation Analysis Kit takes advantage of qPCR testing for rapid and targeted detection, e.g. in endometrial cancer research.

Biomarkers

A456P, P286R , V411L (G>C) and (G>T)

S297F, S459F

Scientific Background

POLE is a human gene encoding the catalytic subunit of the DNA polymerase epsilon complex. Inactivating mutations in the exonuclease domain of POLE lead to impaired proofreading during DNA lead strand replication and consequently to dramatically increased mutation rates of ≥ 100 mut/Mb [2,3].

The pathogenic mutations leading to this ultramutated state have been described in 7-15 % of endometrial and 2-8 % of colorectal cancers. Due to the emerging high mutational burden in the presence of these mutations, pathogenic POLE mutations are currently under clinical evaluation as a predictive marker for admission to immune checkpoint therapy in solid tumors [4].

Moreover, pathogenic POLE mutations are also part of the molecular classification of endometrial cancer, which allows a comprehensive risk assessment of patients and has been implemented in various national and international guidelines (e.g. ESMO, ESP/ESGO, S3) [1].

1. Oaknin, A. et al. Endometrial cancer. ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol 33, 860–877; 10.1016/j.annonc.2022.05.009 (2022).
2. Briggs, S. & Tomlinson, I. Germline and somatic polymerase ε and δ mutations define a new class of hypermutated colorectal and endometrial cancers. J Pathol 230, 148–153; 10.1002/path.4185 (2013).
3. Castellucci, E. et al. DNA Polymerase ɛ Deficiency Leading to an Ultramutator Phenotype. A Novel Clinically Relevant Entity. Oncologist 22, 497–502; 10.1634/theoncologist.2017-0034 (2017).
4. Ma, X. et al. Functional landscapes of POLE and POLD1 mutations in checkpoint blockade-dependent antitumor immunity. Nat Genet 54, 996–1012; 10.1038/s41588-022-01108-w (2022).