Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz

Logo MUG-Forschungsportal

Gewählte Publikation:

SHR Neuro Krebs Kardio Lipid

Aoude, LG; Heitzer, E; Johansson, P; Gartside, M; Wadt, K; Pritchard, AL; Palmer, JM; Symmons, J; Gerdes, AM; Montgomery, GW; Martin, NG; Tomlinson, I; Kearsey, S; Hayward, NK.
POLE mutations in families predisposed to cutaneous melanoma.
Fam Cancer. 2015; 14(4):621-628
Web of Science PubMed FullText FullText_MUG


Autor/innen der Med Uni Graz:
Heitzer Ellen

Dimensions Citations:

Plum Analytics:

Scite (citation analytics):

Germline mutations in the exonuclease domain of POLE have been shown to predispose to colorectal cancers and adenomas. POLE is an enzyme involved in DNA repair and chromosomal DNA replication. In order to assess whether such mutations might also predispose to cutaneous melanoma, we interrogated whole-genome and exome data from probands of 34 melanoma families lacking pathogenic mutations in known high penetrance melanoma susceptibility genes: CDKN2A, CDK4, BAP1, TERT, POT1, ACD and TERF2IP. We found a novel germline mutation, POLE p.(Trp347Cys), in a 7-case cutaneous melanoma family. Functional assays in S. pombe showed that this mutation led to an increased DNA mutation rate comparable to that seen with a Pol ε mutant with no exonuclease activity. We then performed targeted sequencing of POLE in 1243 cutaneous melanoma cases and found that a further ten probands had novel or rare variants in the exonuclease domain of POLE. Although this frequency is not significantly higher than that in unselected Caucasian controls, we observed multiple cancer types in the melanoma families, suggesting that some germline POLE mutations may predispose to a broad spectrum of cancers, including melanoma. In addition, we found the first mutation outside the exonuclease domain, p.(Gln520Arg), in a family with an extensive history of colorectal cancer.
Find related publications in this database (using NLM MeSH Indexing)
Adolescent -
Adult -
Aged -
Aged, 80 and over -
Biomarkers, Tumor - genetics
DNA Polymerase II - genetics
Female -
Follow-Up Studies -
Genetic Predisposition to Disease -
Germ-Line Mutation - genetics
High-Throughput Nucleotide Sequencing -
Humans -
Male -
Melanoma - genetics
Melanoma - pathology
Middle Aged -
Neoplasm Staging -
Pedigree -
Poly-ADP-Ribose Binding Proteins -
Prognosis -
Skin Neoplasms - genetics
Skin Neoplasms - pathology
Young Adult -

Find related publications in this database (Keywords)
Cutaneous melanoma
Germline mutation
© Med Uni Graz Impressum