The landscape of MAP3K1/MAP2K4 alterations in gastrointestinal (GI) malignancies


Matthew K. Stein, Andrew Elliott, Jimmy J. Hwang, Emil Lou, Moh’d M. Khushman, Aaron James Scott, John L. Marshall, Davendra Sohal, Benjamin A. Weinberg, Richard M. Goldberg, Mohamed E. Salem, W. Michael Korn, Axel Grothey


Truncating MAP3K1/MAP2K4 alterations occur in nearly 2% of GI malignancy pts and are more commonly associated with dMMR/MSI-H, higher TMB and other immune biomarkers than WT. • In CRC, MAP3K1/MAP2K4-MT pts had a greater tendency for PIK3CA and APC co-mutation and significantly lower TP53 co-mutation versus WT pts; no difference was seen in BRAF V600E, ERBB2/ERBB3, or KRAS. • Potentially targetable co-mutation partners implicated in PI3K and MAPK pathways as well as POLE, BRCA2 and ATM warrant further evaluation, as well as a high co-mutation rate with ARID1A.

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