Comprehensive profiling of MDM2 amplified gastrointestinal (GI) cancers
Francesca Battaglin, Joanne Xiu, Yasmine Baca, Anthony F. Shields, Richard M. Goldberg, Alberto Puccini, Ryuma Tokunaga, Hiroyuki Arai, Jingyuan Wang, Natsuko Kawanishi, Andreas Seeber, Igor Astaturov, A. Craig Lockhart, Wu Zhang, John L. Marshall, W. Michael Korn, Heinz-Josef Lenz
This is the most extensive profiling study to investigate MDM2 amplified GI tumors.
Our data show distinct molecular patterns of MDM2 amplified GI cancers involving WNT pathway genes, upregulation of FGF signaling and inverse association with TMB and MSI which may explain the resistance mechanisms to ICIs.
TP53 mutations and MDM2 amplification where not mutually exclusive in our cohort, however, lower MDM2 expression was found in TP53-mutated tumors suggesting that TP53 mutational status may impact treatment with MDM2 inhibitors.