A mutation in POLE predisposing to a multi-tumour phenotype
Artikel i vetenskaplig tidskrift, 2014

Somatic mutations in the POLE gene encoding the catalytic subunit of DNA polymerase epsilon have been found in sporadic colorectal cancers (CRCs) and are most likely of importance in tumour development and/or progression. Recently, families with dominantly inherited colorectal adenomas and colorectal cancer were shown to have a causative heterozygous germline mutation in the proofreading exonuclease domain of POLE. The highly penetrant mutation was associated with predisposition to CRC only and no extra-colonic tumours were observed. We have identified a mutation in a large family in which the carriers not only developed CRC, they also demonstrate a highly penetrant predisposition to extra-intestinal tumours such as ovarian, endometrial and brain tumours. The mutation, NM_006231.2:c.1089C>A, p.Asn363Lys, also located in the proofreading exonuclease domain is directly involved in DNA binding. Theoretical prediction of the amino acid substitution suggests a profound effect of the substrate binding capability and a more severe impairment of the catalytic activity compared to the previously reported germline mutation. A possible genotype to phenotype correlation for deleterious mutations in POLE might exist that needs to be considered in the follow-up of mutation carriers.



colorectal cancer

exome sequencing


Anna Rohlin

Göteborgs universitet

Theofanis Zagoras

Göteborgs universitet

Staffan Nilsson

Göteborgs universitet

Chalmers, Matematiska vetenskaper, Matematisk statistik

Ulf Lundstam

Göteborgs universitet

Jan Wahlström

Göteborgs universitet

Leif Hultén

Göteborgs universitet

Tommy Martinsson

Göteborgs universitet

B Göran Karlsson

Göteborgs universitet

Margareta Nordling

Göteborgs universitet

International Journal of Oncology

1019-6439 (ISSN) 17912423 (eISSN)

Vol. 45 1 77-81


Livsvetenskaper och teknik (2010-2018)


Cancer och onkologi



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