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Cell DOI:10.1016/j.cell.2020.10.036

Proteogenomic Landscape of Breast Cancer Tumorigenesis and Targeted Therapy.

Publication TypeJournal Article
Year of Publication2020
AuthorsKrug, K, Jaehnig, EJ, Satpathy, S, Blumenberg, L, Karpova, A, Anurag, M, Miles, G, Mertins, P, Geffen, Y, Tang, LC, Heiman, DI, Cao, S, Maruvka, YE, Lei, JT, Huang, C, Kothadia, RB, Colaprico, A, Birger, C, Wang, J, Dou, Y, Wen, B, Shi, Z, Liao, Y, Wiznerowicz, M, Wyczalkowski, MA, Chen, XSteven, Kennedy, JJ, Paulovich, AG, Thiagarajan, M, Kinsinger, CR, Hiltke, T, Boja, ES, Mesri, M, Robles, AI, Rodriguez, H, Westbrook, TF, Ding, L, Getz, G, Clauser, KR, Fenyö, D, Ruggles, KV, Zhang, B, Mani, DR, Carr, SA, Ellis, MJ, Gillette, MA
Corporate AuthorsClinical Proteomic Tumor Analysis Consortium
JournalCell
Volume183
Issue5
Pages1436-1456.e31
Date Published2020 Nov 25
ISSN1097-4172
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.

DOI10.1016/j.cell.2020.10.036
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/33212010?dopt=Abstract

Alternate JournalCell
PubMed ID33212010