Patterns and regulation of post-translational modifications across cancer

Yifat Geffen ^1,2 Shankara Anand ¹ Yo Akiyama ¹ Tomer M. Yaron ³ Yizhe Song ⁴ Jared L. Johnson ³ Akshay Govindan ⁴ Ozgun Babur Ozgun Babur ² Yize Li ⁴ Emily Huntsman ³ Wang Liang-Bo ⁴ Chet Birger ¹ David I. Heiman ¹ Qing Zhang ¹ Mendy Miller ¹ Yosef E. Maruvka ⁵ Nicholas J Haradhvala ¹ Saveliy Belkin ¹ Alexander Kerelsky ³ Karl R. Clauser ¹ Karsten Krug ¹ Shankha Satpathy ¹ Sam H. Payne ⁶ D. R. Mani ¹ Michael A. Gillette ¹ Saravana M. Dhanasekaran ⁷ Mathangi Thiagarajan ⁸ Mehdi Mesri ⁹ Henry Rodriquez ⁹ Ana I. Robles ⁹ Steven A. Carr ¹ Alexander J. Lazar ¹⁰ Francois Aguet ^1,11 Lewis C. Cantley ³ Li Ding ⁴ Gad Getz ^1,2,12 Analysis Consortium Clinical Proteomic Tumor ⁹

¹Cancer Program, Broad Institute of Massachusetts Institute of Technology and Harvard, USA
²Cancer Center and Department of Pathology,, Massachusetts General Hospital, Boston, USA
³Meyer Cancer Center, Weill Cornell Medical College, USA
⁴School of Medicine, Washington University, USA
⁵Biotechnology and Food Engineering, Lokey Center for Life Science and Engineering, Technion, Israel Institute of Technology Haifa, Israel
⁶Department of Biology, Brigham Young University, USA
⁷Department of Pathology, University of Michigan, USA
⁸Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, USA
⁹Office of Cancer Clinical Proteomics Research, National Cancer Institute, USA
¹⁰Departments of Pathology & Genomic Medicine, The University of Texas MD Anderson Cancer Center, USA
¹¹Illumina Artificial Intelligence Laboratory, Illumina, Inc., USA
¹²Department of Pathology, Harvard Medical School, USA

Post-translational modifications (PTMs) play key roles in regulating cell signaling and physiology both in normal and cancer cells. Advances in mass spectrometry enable high-throughput, accurate and sensitive measurement of PTM levels to better understand their role, prevalence, and crosstalk. In cancer, previous studies of PTMs focused on a single cancer type. Here, we analyze the largest collection of genomic, transcriptomic, proteomic, and PTM profiles compiled from 10 cancer types characterized by the National Cancer Institute`s Clinical Proteomic Tumor Analysis Consortium (CPTAC). Our study reveals Pan-Cancer patterns of PTMs associated with changes in protein acetylation and phosphorylation involved in different cancer processes. These patterns highlight subsets of tumors, from different cancer types, with dysregulated DNA repair, altered metabolic regulation associated with immune response, patterns of acetylation that affect kinase specificity, and altered histone regulation. Overall, this resource highlights the rich biology governed by PTMs and exposes potential new therapeutic avenues.