Proteogenomic landscape of breast cancer tumorigenesis and targeted therapy
- Krug, K.
- Jaehnig, E.J.
- Satpathy, S.
- Blumenberg, L.
- Karpova, A.
- Anurag, M.
- Miles, G.
- Mertins, P.
- Geffen, Y.
- Tang, L.C.
- Heiman, D.I.
- Cao, S.
- Maruvka, Y.E.
- Lei, J.T.
- Huang, C.
- Kothadia, R.B.
- Colaprico, A.
- Birger, C.
- Wang, J.
- Dou, Y.
- Wen, B.
- Shi, Z.
- Liao, Y.
- Wiznerowicz, M.
- Wyczalkowski, M.A.
- Chen, X.S.
- Kennedy, J.J.
- Paulovich, A.G.
- Thiagarajan, M.
- Kinsinger, C.R.
- Hiltke, T.
- Boja, E.S.
- Mesri, M.
- Robles, A.I.
- Rodriguez, H.
- Westbrook, T.F.
- Ding, L.
- Getz, G.
- Clauser, K.R.
- Fenyö, D.
- Ruggles, K.V.
- Zhang, B.
- Mani, D.R
- Carr, S.A.
- Ellis, M.J.
- Gillette, M.A.
DOIAbstract
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 analys...
