Human Oncology & Pathogenesis Program
The Marc Ladanyi Lab
The research program in this laboratory focuses on the genomics and molecular pathogenesis of sarcomas and thoracic malignancies, with an emphasis on clinical translation of potential diagnostic markers and therapeutic targets. Dr. Ladanyi also co-directs (with Chris Sander) the Genome Data Analysis Center at Memorial Sloan Kettering, which is part of the TCGA project network.
Examples of recent contributions include the validation of DUSP4 as a driver gene for 8p losses in EGFR-mutant lung adenocarcinomas, the establishment of methods for enhanced detection of the EGFR T790M secondary mutation in the setting of acquired resistance to EGFR inhibitors, the discovery of BAP1 mutations in mesotheliomas with 3p losses, the identification of novel, recurrent HEY1-NCOA2 and KIF5B-RET fusions in mesenchymal chondrosarcoma and lung adenocarcinoma, respectively, both based on mining of exon-level expression data, as well as major involvement in the TCGA Network marker papers on the genomics of glioblastoma, ovarian carcinoma, and squamous lung cancer. Ongoing projects are addressing further questions in lung adenocarcinoma, mesothelioma, and several sarcoma types using whole exome and whole transcriptome sequencing, ChIP-seq, Sequenom mass spectrometry genotyping, NanoString expression profiling, RNAi screens, chemical screens, and proteomic approaches.
Hayashi T, Desmeules P, Smith RS, Drilon A, Somwar R, Ladanyi M. (2018). RASA1 and NF1 are Preferentially Co-Mutated and Define A Distinct Genetic Subset of Smoking-Associated Non-Small Cell Lung Carcinomas Sensitive to MEK Inhibition. Clinical cancer research : an official journal of the American Association for Cancer Research, 24(6), 1436–1447.
Fan PD, Narzisi G, Jayaprakash AD, Venturini E, Robine N, Smibert P, Germer S, Yu HA, Jordan EJ, Paik PK, Janjigian YY, Chaft JE, Wang L, Jungbluth AA, Middha S, Spraggon L, Qiao H, Lovly CM, Kris MG, Riely GJ, Politi K, Varmus H, Ladanyi M. (2018). YES1 amplification is a mechanism of acquired resistance to EGFR inhibitors identified by transposon mutagenesis and clinical genomics. Proceedings of the National Academy of Sciences of the United States of America, 115(26), E6030–E6038.
Shukla N, Somwar R, Smith RS, Ambati S, Munoz S, Merchant M, D’Arcy P, Wang X, Kobos R, Antczak C, Bhinder B, Shum D, Radu C, Yang G, Taylor BS, Ng CK, Weigelt B, Khodos I, de Stanchina E, Reis-Filho JS, Ouerfelli O, Linder S, Djaballah H, Ladanyi M. (2016). Proteasome Addiction Defined in Ewing Sarcoma Is Effectively Targeted by a Novel Class of 19S Proteasome Inhibitors. Cancer research, 76(15), 4525–4534.
Marc Ladanyi, MD
- Molecular pathologist Marc Ladanyi studies the molecular pathogenesis of sarcomas, lung cancer, and mesothelioma.
- MD, McGill University