Article
Mutations in the RAS/MAPK Pathway Drive Replication Repair-Deficient Hypermutated Tumors and Confer Sensitivity to MEK Inhibition.
Cancer discovery - 1 Jun 2021
Campbell Brittany B, Galati Melissa A, Stone Simone C, Riemenschneider Alexandra N, Edwards Melissa, Sudhaman Sumedha, Siddaway Robert, Komosa Martin, Nunes Nuno M, Nobre Liana, Morrissy A Sorana, Zatzman Matthew, Zapotocky Michal, Joksimovic Lazar, Kalimuthu Sangeetha N, Samuel David, Mason Gary, Bouffet Eric, Morgenstern Daniel A, Aronson Melyssa, Durno Carol, Malkin David, Maris John M, Taylor Michael D, Shlien Adam, Pugh Trevor J, Ohashi Pamela S, Hawkins Cynthia E, Tabori Uri
Abstract excerpt
The RAS/MAPK pathway is an emerging targeted pathway across a spectrum of both adult and pediatric cancers. Typically, this is associated with a single, well-characterized point mutation in an oncogene. Hypermutant tumors that harbor many somatic mutations may obscure the interpretation of such targetable genomic events. We find that replication repair-deficient (RRD) cancers, which are universally hypermutant...
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