A functional taxonomy of tumor suppression in oncogenic KRAS-driven lung cancer
Authors listHongchen Cai Su Kit Chew Chuan Li Min K Tsai Laura Andrejka Christopher W Murray Nicholas W Hughes Emily G Shuldiner Emily L Ashkin Rui Tang King L Hung Leo C Chen Shi Ya C Lee Maryam Yousefi Wen-Yang Lin Christian A Kunder Le Cong Christopher D McFarland Dmitri A Petrov Charles Swanton Monte M Winslow
Cancer genotyping has identified a large number of putative tumor suppressor genes. Carcinogenesis is a multi-step process, however the importance and specific roles of many of these genes during tumor initiation, growth and progression remain unknown. Here we use a multiplexed mouse model of oncogenic KRAS-driven lung cancer to quantify the impact of forty-eight known and putative tumor suppressor genes on diverse aspects of carcinogenesis at an unprecedented scale and resolution. We uncover many previously understudied functional tumor suppressors that constrain cancer in vivo. Inactivation of some genes substantially increased growth, while the inactivation of others increases tumor initiation and/or the emergence of exceptionally large tumors. These functional in vivo analyses revealed an unexpectedly complex landscape of tumor suppression that has implications for understanding cancer evolution, interpreting clinical cancer genome sequencing data, and directing approaches to limit tumor initiation and progression.
Journal Cancer Discovery
Pages Epub ahead of print