Modaplex POLE/POLD1 Mutation Analysis Kit

With the Modaplex POLE/POLD1 Mutation Analysis Kit clinical research laboratories have access to results in 3.5 hours after nucleic acid preparation.

The Modaplex POLE/POLD1 Mutation Analysis Assays is to be used with the Modaplex instrument platform version 1.0 or higher. Thus, the POLE/POLD1 workflow is similar to the workflow of other Biotype Modaplex assays such as MSI Analysis Assay and comprises the same three steps after nucleic acid preparation: PCR set up, Modaplex run, and result interpretation.

Investigate POLE Mutations in Endometrium

Exonuclease domain mutations (EDMs) of DNA polymerase epsilon and delta subunit epsilon can lead to impair proofreading during DNA replication, thereby increase dramatically the mutation rates and promotes tumorigeneses.

DNA polymerase Epsilon (POLE) exonuclease domain mutations characterize a subtype of endometrial cancer (EC) with a markedly increased somatic mutational burden. POLE-mutant tumors were described as a molecular subtype with improved progression-free survival by The Cancer Genome Atlas [1]. Based on integrated genomic characterization, endometrial cancer was classified as POLE ultramutated, MSI hypermutated, and copynumber low and high subtypes. Molecular classification is encouraged in all endometrial carcinomas, especially high-grade tumors are recommended by ESGO/ESTRO/ESP guidelines [2] for the management of patients with endometrial carcinoma.

POLE and POLD1 EDMs as Research Marker for Immune checkpoint Inhibition

MSI testing is a promising approach to determine the response to immune checkpoint inhibitors for gastrointestinal tract and endometrial tissue tumor entities [3, 4, 5]. But in fact, detecting the MSS stable phenotype excludes patients from MSI-associated therapies. Studies have shown that somatic POLE mutations are associated with MSS and hypermutated phenotypes in colorectal and endometrial tumors [6, 7]. Therefore, somatic POLE EDMs may be promising candidates for decision-making by immune checkpoint therapy [7, 8].

References

1. Levine, D. & The Cancer Genome Atlas Research Network Integrated genomic characterization of endometrial carcinoma. Nature 2013, 497, 67–73.
2. Concin, N.; Matias-Guiu, X.; Vergote, I.; Cibula, D.; Mirza, M.R.; Marnitz, S.; Ledermann, J.; Bosse, T.; Chargari, C.; Fagotti, A.; et al. ESGO/ESTRO/ESP Guidelines for the management of patients with endometrial carcinoma. Virchows Arch. 2021, 478, 153–190.
3. D.T. Le et al, “Mismatch-repair deficiency predicts response of solid tumors to PD-1 blockade”, Science, vol. 357, no. 6349, pp. 409-413, 2017.
4. Z.R. Chalmers et al, “Analysis of 100,000 human cancer genomes reveals the landscape of tumor mutational burden”, Genome Medicine, vol. 9, no. 34, 2017.
5. H. Westdorp et al, “Opportunities for immunotherapy in microsatellite instable colorectal cancer”, Cancer Immunol. Immunother. vol. 65, no. 10, pp. 1249-1259, 2016.
6. R. Bourdais et al, “Polymerase proofreading domain mutations: New opportunities for immunotherapy in hypermutated colorectal cancer beyond MMR deficiency”, Crit. Rev. Oncol. Hematol., vol. 113, pp. 242-248, 2017.
7. J.M. Mehnert et al, “Immune activation and response to pembrolizumab in POLE-mutant endometrial cancer”, J. Clin. Invest., vol. 126, no. 6, pp. 2334-2340, 2016.
8. J. Gong et al, “Response to PD-1 Blockade in Microsatellite Stable Metastatic Colorectal Cancer Harboring a POLE Mutation”, J. Nati. Compr. Canc. Netw., vol. 15, no. 2, pp. 142-147, 2017.

If there are questions or feedback on how POLE testing with Modaplex can improve your research activity don’t hesitate to contact us at: support@biotype.de

To order the Modaplex POLE/POLD1 Mutation Analysis Kit, please e-mail us at sales@biotype.de

Modaplex POLE/POLD1 Mutation Analysis Kit Brochure
Modaplex POLE/POLD1 Mutation Analysis Kit Instructions for Use (IFU)
Modaplex Brochure