Genome-wide chemical mutagenesis screens allow unbiased saturation of the cancer genome and identification of drug resistance mutations

Mostra el registre complet Registre parcial de l'ítem

• dc.contributor.author Brammeld, Jonathan S.ca
• dc.contributor.author Dalmases Massegú, Alba, 1982-ca
• dc.contributor.author Bellosillo Paricio, Beatrizca
• dc.contributor.author Vidal Barrull, Joanaca
• dc.contributor.author Montagut Viladot, Claraca
• dc.contributor.author McDermott, Ultanca
• dc.date.accessioned 2018-01-16T08:18:55Z
• dc.date.available 2018-01-16T08:18:55Z
• dc.date.issued 2017
• dc.description.abstract 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.
• dc.format.mimetype application/pdfca
• dc.identifier.citation Brammeld JS, Petljak M, Martincorena I, Williams SP, Alonso LG, Dalmases A. et al. Genome-wide chemical mutagenesis screens allow unbiased saturation of the cancer genome and identification of drug resistance mutations. Genome Res. 2017 Apr;27(4):613-625. DOI: 10.1101/gr.213546.116
• dc.identifier.doi http://dx.doi.org/10.1101/gr.213546.116
• dc.identifier.issn 1088-9051
• dc.identifier.uri http://hdl.handle.net/10230/33633
• dc.language.iso eng
• dc.publisher Cold Spring Harbor Laboratory Press (CSHL Press)ca
• dc.relation.ispartof Genome Research. 2017 Apr;27(4):613-25
• dc.rights Published originally by Cold Spring Harbor Laboratory Press at 10.1101/gr.213546.116. Beginning six months from the full-issue publication date, articles are distributed under the Creative Commons Attribution-Non-Commercial 4.0 International License (CC-BY-NC), as described at http://creativecommons.org/licenses/by-nc/4.0/. This license permits non-commercial use, including reproduction, adaptation, and distribution of the article provided the original author and source are credited.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.subject.other Càncer -- Aspectes genètics
• dc.subject.other Medicaments -- Efectes secundaris
• dc.title Genome-wide chemical mutagenesis screens allow unbiased saturation of the cancer genome and identification of drug resistance mutationsca
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/acceptedVersion