POLE somatic mutations in advanced colorectal cancer

Cancer Medicine
Joana GuerraManuel R Teixeira

Abstract

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 biol...Continue Reading

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Citations

Jul 11, 2019·Nature Reviews. Clinical Oncology·Anita SveenRagnhild A Lothe
Jan 17, 2019·Journal of Personalized Medicine·Jai N PatelMegan Jagosky
Jun 5, 2019·Cold Spring Harbor Molecular Case Studies·Toni Rose JueKerrie L McDonald
Dec 28, 2019·Mutagenesis·Isabel Alvarado-CruzJoann Balazs Sweasy
Jul 28, 2019·Pediatric Blood & Cancer·Oren Levine, Kevin Zbuk
Dec 22, 2020·European Journal of Pharmacology·Chandra Kishore, Priyanka Bhadra
Aug 19, 2020·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Arndt StahlerVolker Heinemann
Apr 14, 2021·Seminars in Cancer Biology·Pietro AndreiAlberto Bardelli

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Methods Mentioned

BETA
exome sequencing
PCR

Software Mentioned

Primer
BLAST
GeneMapper

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