美国博德研究所Michael A. Gillette等研究人员合作绘制出乳腺癌肿瘤发生和靶向治疗的蛋白基因组学图谱。相关论文于2020年11月18日在线发表在《细胞》杂志上。
Title: Proteogenomic Landscape of Breast Cancer Tumorigenesis and Targeted Therapy
Author: Karsten Krug, Eric J. Jaehnig, Shankha Satpathy, Lili Blumenberg, Alla Karpova, Meenakshi Anurag, George Miles, Philipp Mertins, Yifat Geffen, Lauren C. Tang, David I. Heiman, Song Cao, Yosef E. Maruvka, Jonathan T. Lei, Chen Huang, Ramani B. Kothadia, Antonio Colaprico, Chet Birger, Jarey Wang, Yongchao Dou, Bo Wen, Zhiao Shi, Yuxing Liao, Maciej Wiznerowicz, Matthew A. Wyczalkowski, Xi Steven Chen, Jacob J. Kennedy, Amanda G. Paulovich, Mathangi Thiagarajan, Christopher R. Kinsinger, Tara Hiltke, Emily S. Boja, Mehdi Mesri, Ana I. Robles, Henry Rodriguez, Thomas F. Westbrook, Li Ding, Gad Getz, Karl R. Clauser, David Feny, Kelly V. Ruggles, Bing Zhang, D.R. Mani, Steven A. Carr, Matthew J. Ellis, Michael A. Gillette, Shayan C. Avanessian, Shuang Cai, Daniel Chan, Xian Chen, Nathan J. Edwards, Andrew N. Hoofnagle, M. Harry Kane, Karen A. Ketchum, Eric Kuhn, Douglas A. Levine, Shunqiang Li, Daniel C. Liebler, Tao Liu, Jingqin Luo, Subha Madhavan, Chris Maher, Jason E. McDermott, Peter B. McGarvey, Mauricio Oberti, Akhilesh Pandey, Samuel H. Payne, David F. Ransohoff, Robert C. Rivers, Karin D. Rodland, Paul Rudnick, Melinda E. Sanders, Kenna M. Shaw, Ie-Ming Shih, Robbert J.C. Slebos, Richard D. Smith, Michael Snyder, Stephen E. Stein, David L. Tabb
Abstract: The integration of mass spectrometry-based proteomics with next-generation DNA and RNA sequencing profiles tumors more comprehensively. Here this “proteogenomics” approach was applied to 122 treatment-naive primary breast cancers accrued to preserve post-translational modifications, including protein phosphorylation and acetylation. Proteogenomics challenged standard breast cancer diagnoses, provided detailed analysis of the ERBB2 amplicon, defined tumor subsets that could benefit from immune checkpoint therapy, and allowed more accurate assessment of Rb status for prediction of CDK4/6 inhibitor responsiveness. Phosphoproteomics profiles uncovered novel associations between tumor suppressor loss and targetable kinases. Acetylproteome analysis highlighted acetylation on key nuclear proteins involved in the DNA damage response and revealed cross-talk between cytoplasmic and mitochondrial acetylation and metabolism. Our results underscore the potential of proteogenomics for clinical investigation of breast cancer through more accurate annotation of targetable pathways and biological features of this remarkably heterogeneous malignancy.