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07.09.2018 | Original Article – Cancer Research | Ausgabe 11/2018

Journal of Cancer Research and Clinical Oncology 11/2018

POLE gene hotspot mutations in advanced pancreatic cancer

Zeitschrift:
Journal of Cancer Research and Clinical Oncology > Ausgabe 11/2018
Autoren:
Michael Guenther, Vivien Veninga, Joerg Kumbrink, Michael Haas, C. Benedikt Westphalen, Stephan Kruger, Volker Heinemann, Thomas Kirchner, Stefan Boeck, Andreas Jung, Steffen Ormanns
Wichtige Hinweise

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1007/​s00432-018-2746-x) contains supplementary material, which is available to authorized users.

Abstract

Purpose

Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease, lacking relevant prognostic and predictive biomarkers. DNA polymerase epsilon (POLE) has important functions in the maintenance of genetic stability during DNA replication and has previously been associated with favorable prognosis in endometrial and colorectal cancer. However, its relevance in advanced pancreatic cancer (aPDAC) has not been examined to date.

Methods

Using pyrosequencing on tumoral DNA extracted from 60 samples from the AIO-PK0104 study as well as 55 samples from completed translational trials, we examined POLE hotspot mutations in exon 9 (P286R) and exon 13 (V411R/L/M) in the POLE gene exonuclease domain. DNA extracted from 37 endometrial carcinomas were tested as positive controls. Publically available sequencing databases were searched for POLE mutations in PDAC samples.

Results

Fifty-three patients (pts) were men, 62 pts were women, median age was 61.2 years. Median overall survival (OS) was 7.4 months and median progression free survival (PFS) was 4.0 months. In four of the 37 endometrial carcinomas POLE mutations were detected in exon 9 (10.8%) and none in exon 13. In none of the overall 115 aPDAC tumors POLE gene hotspot mutations could be detected.

Conclusion

Mutations in the hotspot regions of exon 9 and 13 of the POLE gene are very rare events in advanced pancreatic cancer. Thus, it is unlikely that POLE gene mutations contribute to genetic instability in the vast majority of aPDAC. POLE mutation does not serve as a relevant biomarker and should not be tested on a regular basis in PDAC.

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