POLE somatic mutations in advanced colorectal cancer

• Type: Article in International Scientific Journal
• Date: 2017

Authors

Guerra, J (Author) Other; Pinto, C (Author) Other; Pinto, D (Author) Other; Pinheiro, M (Author) Other; Silva, R (Author) Other; Peixoto, A (Author) Other; Rocha, P (Author) Other; Veiga, I (Author) Other; Santos, C (Author) Other; Santos, R (Author) Other; Cabreira, V (Author) Other; Lopes, P (Author) Other; henrique, rmf (Author) ICBAS; Manuel R Teixeira (Author) ICBAS

Journal

The Journal is awaiting validation by the Administrative Services.

Title: CANCER MEDICINE

Vol. 6

Pages: 2966-2971

ISSN: 2045-7634

Indexing

ISI Web of Knowledge - 36 Citations

Scopus - 34 Citations

Other information

Authenticus ID: P-00N-BBM

DOI: 10.1002/cam4.1245

Abstract (EN): Despite all the knowledge already gathered, the picture of somatic genetic changes in colorectal tumorigenesis is far from complete. Recently, germline and somatic mutations in the exonuclease domain of polymerase epsilon, catalytic subunit (POLE) gene have been reported in a small subset of microsatellite-stable and hypermutated colorectal carcinomas (CRCs), affecting the proofreading activity of the enzyme and leading to misincorporation of bases during DNA replication. To evaluate the role of POLE mutations in colorectal carcinogenesis, namely in advanced CRC, we searched for somatic mutations by Sanger sequencing in tumor DNA samples from 307 cases. Microsatellite instability and mutation analyses of a panel of oncogenes were performed in the tumors harboring POLE mutations. Three heterozygous mutations were found in two tumors, the c.857C>G, p.Pro286Arg, the c.901G>A, p.Asp301Asn, and the c.1376C>T, p.Ser459Phe. Of the POLE-mutated CRCs, one tumor was microsatellite-stable and the other had low microsatellite instability, whereas KRAS and PIK3CA mutations were found in one tumor each. We conclude that POLE somatic mutations exist but are rare in advanced CRC, with further larger studies being necessary to evaluate its biological and clinical implications.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 6