Article
Cancers from Novel Pole-Mutant Mouse Models Provide Insights into Polymerase-Mediated Hypermutagenesis and Immune Checkpoint Blockade.
Cancer research - 15 Dec 2020
Galati Melissa A, Hodel Karl P, Gams Miki S, Sudhaman Sumedha, Bridge Taylor, Zahurancik Walter J, Ungerleider Nathan A, Park Vivian S, Ercan Ayse B, Joksimovic Lazar, Siddiqui Iram, Siddaway Robert, Edwards Melissa, de Borja Richard, Elshaer Dana, Chung Jiil, Forster Victoria J, Nunes Nuno M, Aronson Melyssa, Wang Xia, Ramdas Jagadeesh, Seeley Andrea, Sarosiek Tomasz, Dunn Gavin P, Byrd Jonathan N, Mordechai Oz, Durno Carol, Martin Alberto, Shlien Adam, Bouffet Eric, Suo Zucai, Jackson James G, Hawkins Cynthia E, Guidos Cynthia J, Pursell Zachary F, Tabori Uri
Abstract excerpt
POLE mutations are a major cause of hypermutant cancers, yet questions remain regarding mechanisms of tumorigenesis, genotype-phenotype correlation, and therapeutic considerations. In this study, we establish mouse models harboring cancer-associated POLE mutations P286R and S459F, which cause rapid albeit distinct time to cancer initiation in vivo, independent of their exonuclease activity. Mouse and human...
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