2011 UALC
Marc Ladanyi, MD
Memorial Sloan Kettering Cancer Center
Research Project:
Beyond EGFR, KRAS, and ALK: mining mutation data from whole exome sequencing of lung adenocarcinomas negative for all known driver oncogenes
Summary:
Dr. Ladanyi has shown that up to 66% of lung adenocarcinomas contain known ‘driver’ oncogenes (EGFR, ALK, KRas, HER2, etc), and these mutations are mutually exclusive (they are never found together in the same cancer cells). However, that leaves 33% of cases without any known ‘driver’. Dr. Ladanyi has assembled a set of over 60 lung cancers without any known driver oncogenes and is using the most current DNA sequencing technologies (complementary to Dr. Chen’s project) to screen every gene in these 60 tumors for mutations. In this study, Dr. Ladanyi will validate these new mutations as true ongenic drivers and investigate how these mutations cause lung tumors to grow.
More Content:
Interim Report
Dr. Ladanyi’s team has been mining a vast array of data, including combining their experimental data with publicly available data-sets from The Cancer Genome Atlas and the Broad Institute. They have identified two additional genetic alterations, mutually exclusive to the current known driver mutations found in lung adenocarcinomas. They are currently performing the functional studies to understand how these genes affect growth signaling pathways in lung cancers to determine how we can target them therapeutically. In addition, they have identified additional types of mutations in a known driver oncogene, MAP2K1, and are characterizing these rare changes. Unexpectedly, Dr. Ladanyi’s team also found a subset of lung cancers with a very high burden of somatic mutations. Normally, lung adenocarcinomas have about 400 somatic mutations, this subset can show 1500-2500 mutations. The team is further analyzing the differences in these subsets of tumors to give new insights into treatment strategies.