In summary, combining multi-platform data from WES, RNA-Seq and global proteomics, we confirmed the dominant role of RET and RAS mutations in MTC and identified potential driver alterations (BRAF, NF1) that were mutually exclusive to RET and RAS. Ultimately, we have identified putative cancer drivers in 93/102 MTCs (91.2%) in our cohort, reducing the proportion of “dark matter” cases from 18.3% in a previous study to 8.8% in our present work25. Here, NF1 is linked to cancer.