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.
journal_name
Celljournal_title
Cellauthors
Krug 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,Wizndoi
10.1016/j.cell.2020.10.036subject
Has Abstractpub_date
2020-11-25 00:00:00pages
1436-1456.e31issue
5eissn
0092-8674issn
1097-4172pii
S0092-8674(20)31400-8journal_volume
183pub_type
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