Double strand break repair components are frequent targets of microsatellite instability in endometrial cancer

European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)
Cristina BilbaoJuan Carlos Díaz-Chico

Abstract

DNA double strand break (DSB) repair is a central cellular mechanism of the DNA damage response to maintain genomic stability. DSB components are frequently mutated in colorectal cancer with microsatellite instability (MSI). We investigated whether DSB repair is involved in endometrial cancer (EC) with MSI. Mononucleotide microsatellite tracts of 14 genes of the DSB repair system were analysed in a series of 41 EC with MSI. Among these genes, the microcephalin 1 (MCPH1/BRIT1) has never been tested as target of MSI in tumour series. The most frequently mutated gene was DNAPKcs (n=14, 34%) followed by RAD50 (n=7, 17%), MRE11, ATR and BRCA1 (n=6, 15%), and by CtIP and MCPH1 (n=5, 12%). While DSB biallelic mutations were infrequent, a high proportion of tumours (n=30, 73%) presented mutations at some component of the DSB repair pathway, and almost half of them showed alterations at two or more components. Tumours with mutations in two or more genes were significantly associated with advanced grade (p=0.03) and vascular invasion (p=0.02) and marginally associated with advanced stage (p=0.07). Our results suggest that in EC, the DSB repair is a relatively common mutational target of MSI and might contribute to tumour progression, and...Continue Reading

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Citations

Nov 3, 2012·Annals of Surgical Oncology·Nilanjana BhattacharyaChinmay Kumar Panda
Jun 14, 2014·PloS One·Romana KoppensteinerKonstantin J Dedes
Feb 25, 2014·European Journal of Cell Biology·Thejaswini Venkatesh, Padmanaban S Suresh
Dec 19, 2013·Pathology Oncology Research : POR·Ewa FormaAnna Krześlak
Jan 10, 2014·Cancer Medicine·Isabel Soria-BretonesPablo Huertas
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Oct 4, 2019·Molecular Carcinogenesis·Mitsuhiro TsuboiAkira Tangoku
Sep 21, 2020·Seminars in Cell & Developmental Biology·Nour L MozaffariAlessandro A Sartori

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