P37: POLE mutations – The growing cancer specter and need for surveillance protocols

Anna Elisabeth Sylvander1, Wenche Sjursen1,2,  Inga Bjørnevoll1

1 – Department of Pathology and Medical Genetics, St. Olavs University Hospital, Trondheim Norway. 2 – Department of Laboratory Medicine Children’s and Women’s Health, Norwegian University of Science and Technology, Trondheim  Norway.


Background: Polymerase proofreading associated polyposis syndrome (PPAP) is a newly described colorectal syndrome and is caused by germline mutations in the POLE and POLD1 genes. Individuals with PPAP have a high risk of developing colorectal adenomas and carcinomas in several organs. Surveillance guidelines regarding management of mutation carriers do not yet exist. In this study we aim to investigate the clinical (phenotype) characteristics of this syndrome to help establish the clinical management.


Participants from two Norwegian families with a mutation in the POLE gene were included in this study. Patient information such as mutation type, age at diagnosis, presence of polyps and cancer type was extracted.


Results: In the family described we observe a large phenotypic variation among the mutation carriers. In addition to colorectal adenomas, we report a broader cancer spectrum with cancer in colon, rectum, small intestine, pancreas and ovaries (bilateral). This study also reveals early onset uterine and pancreatic cancer and esophageal and gastric polyps.


The findings in this study present the broad cancer specter and complexity of clinical management in PPAP. This confirms the need for international surveillance protocols.