Kent Mouw Shares the Results of a Study on ERCC2 Mutations And Cisplatin Sensitivity
Kent Mouw, Radiation Oncologist at Brigham and Women’s Hospital and Associate Professor at Harvard Medical School, shared an article by Judit Börcsök et al. published in The Journal of Clinical Investigation on X, adding:
”Happy to share our results from a fun collaborative effort recently published in the Journal of Clinical Investigation.
“Quantitative functional profiling of ERCC2 mutations deciphers cisplatin sensitivity in bladder cancer”
A brief overview of our findings…
First of all, this was a huge collaborative effort co-led by the Sorensen lab University of Copenhagen Research and Szallasi lab Boston Children’s with important contributions from Lars Dyrskjøt, Aarhus Universitet, Gopa Iyer, Brendan Guercio, Memorial Sloan Kettering Cancer Center, and others….
We assembled a multi-institutional cohort of >2000 MIBCs and comprehensively mapped the ERCC2 mutational landscape. ERCC2 helicase domain mutations were assoc with improved survival in patients treated with neoadjuvant chemotherapy, but not in patients with metastatic dx…
Next, we applied a high-throughput CRISPR-based functional assay (CRISPR-Select) developed in the Sorensen lab to test the impact of ERCC2 mutations on cisplatin sensitivity…
Title: Multiparametric and accurate functional analysis of genetic sequence variants using CRISPR-Select
Authors: Yiyuan Niu, Catarina A. Ferreira Azevedo, Xin Li, Elahe Kamali, Ole Haagen Nielsen, Claus Storgaard Sørensen, Morten Frödin
Read the Full Article here.
We validated and extended our previous findings that only mutations in the helicase domain sensitize to cisplatin…
Importantly, we also adapted the CRISPR-Select assay to introduce heterozygous ERCC2 mutations (how they occur in patients!) and show that these het ERCC2 mutations are sufficient to drive cisplatin sensitivity…
Finally, we compared our functional data to several computational predictors of pathogenicity…although helicase domain mutations were more likely to be predicted pathogenic, there were significant discrepancies, highlighting the important role of functional approaches.”
Title: Quantitative functional profiling of ERCC2 mutations deciphers cisplatin sensitivity in bladder cancer
Authors: Judit Börcsök, Diyavarshini Gopaul, Daphne Devesa-Serrano, Clémence Mooser, Nicolas Jonsson, Matteo Cagiada, Dag R. Stormoen, Maya N. Ataya, Brendan J. Guercio, Hristos Z. Kaimakliotis, Gopa Iyer, Kresten Lindorff-Larsen, Lars Dyrskjøt, Kent W. Mouw, Zoltan Szallasi, Claus S. Sørensen
Read the Full Article.
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