2026-04-13T13:24:50Zhttps://recercat.cat/oai/request
oai:recercat.cat:2072/4613442025-04-03T07:54:21Zcom_2072_98col_2072_378192
RECERCAT author Brammeld, Jonathan S. author Petljak, Mia author Martincorena, Inigo author Williams, Steven P. author Garcia-Alonso, Luz author Dalmases, Alba author Bellosillo Paricio, Beatriz author Robles-Espinoza, Carla Daniela author Price, Stacey author Barthorpe, Syd author Tarpey, Patrick author Alifrangis, Constantine author Bignell, Graham author Vidal, Joana author Young, Jamie author Stebbings, Lucy author Beal, Kathryn author Stratton, Michael R. author Saez-Rodriguez, Julio author Garnett, Mathew author Montagut, Clara author Iorio, Francesco author McDermott, Ultan author Universitat Autònoma de Barcelona 2017 Drug resistance is an almost inevitable consequence of cancer therapy and ultimately proves fatal for the majority of patients. In many cases, this is the consequence of specific gene mutations that have the potential to be targeted to resensitize the tumor. The ability to uniformly saturate the genome with point mutations without chromosome or nucleotide sequence context bias would open the door to identify all putative drug resistance mutations in cancer models. Here, we describe such a method for elucidating drug resistance mechanisms using genome-wide chemical mutagenesis allied to next-generation sequencing. We show that chemically mutagenizing the genome of cancer cells dramatically increases the number of drug-resistant clones and allows the detection of both known and novel drug resistance mutations. We used an efficient computational process that allows for the rapid identification of involved pathways and druggable targets. Such a priori knowledge would greatly empower serial monitoring strategies for drug resistance in the clinic as well as the development of trials for drug-resistant patients. open access Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. https://creativecommons.org/licenses/by/4.0/ Genome-wide chemical mutagenesis screens allow unbiased saturation of the cancer genome and identification of drug resistance mutations Article