POLE gene hotspot mutations in advanced pancreatic cancer View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2018-11

AUTHORS

Michael Guenther, Vivien Veninga, Joerg Kumbrink, Michael Haas, C. Benedikt Westphalen, Stephan Kruger, Volker Heinemann, Thomas Kirchner, Stefan Boeck, Andreas Jung, Steffen Ormanns

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. More... »

PAGES

2161-2166

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s00432-018-2746-x

DOI

http://dx.doi.org/10.1007/s00432-018-2746-x

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1106835560

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30194485


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curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1007/s00432-018-2746-x'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1007/s00432-018-2746-x'

RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1007/s00432-018-2746-x'


 

This table displays all metadata directly associated to this object as RDF triples.

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