Dataset Information

Proteogenomic Landscape of Breast Cancer Tumorigenesis and Targeted Therapy.

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.

SUBMITTER: Krug K

PROVIDER: S-EPMC8077737 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Proteogenomic Landscape of Breast Cancer Tumorigenesis and Targeted Therapy.

Krug Karsten K Jaehnig Eric J EJ Satpathy Shankha S Blumenberg Lili L Karpova Alla A Anurag Meenakshi M Miles George G Mertins Philipp P Geffen Yifat Y Tang Lauren C LC Heiman David I DI Cao Song S Maruvka Yosef E YE Lei Jonathan T JT Huang Chen C Kothadia Ramani B RB Colaprico Antonio A Birger Chet C Wang Jarey J Dou Yongchao Y Wen Bo B Shi Zhiao Z Liao Yuxing Y Wiznerowicz Maciej M Wyczalkowski Matthew A MA Chen Xi Steven XS Kennedy Jacob J JJ Paulovich Amanda G AG Thiagarajan Mathangi M Kinsinger Christopher R CR Hiltke Tara T Boja Emily S ES Mesri Mehdi M Robles Ana I AI Rodriguez Henry H Westbrook Thomas F TF Ding Li L Getz Gad G Clauser Karl R KR Fenyö David D Ruggles Kelly V KV Zhang Bing B Mani D R DR Carr Steven A SA Ellis Matthew J MJ Gillette Michael A MA

Cell 20201118 5

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 ch ...[more]

PMID: 33212010

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Project description:Karsten Krug, Eric J. Jaehnig, Shankha Satpathy, Lili Blumenberg, Alla Karpova, Meenakshi Anurag et al., (2020) <a href="https://www.cell.com/cell/fulltext/S0092-8674(20)31400-8" target="_blank">Cell, 183, 1436-1456</a> DOI: https://doi.org/10.1016/j.cell.2020.10.036 The integration of mass spectrometry-based proteomics with next-generation DNA and RNA sequencing profiles tumors more comprehensively. Herein this "proteogenomic" approach was applied to 122 treatment-naive primary breast cancers purposely 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 the prediction of CDK4/6 inhibitor responsiveness. Phosphoproteomic 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 the clinical investigation of breast cancer through more accurate annotation of targetable pathways and biological features of this remarkably heterogeneous malignancy.Genomic Data for Breast Cancer tumors is available from the NCI Genomic Data Commons (GDC), <a href="https://portal.gdc.cancer.gov/projects/CPTAC-2" target="_blank">here</a> Gene Expression data in GCT file format is available under the metadata section below Proteomic Data Analysis for Breast Cancer tumors (PSMs and Summary Reports) is available from the CPTAC Common Data Analysis Pipeline (Study S039 Early Data Release), <a href="/study-summary/S039" target="_blank">here</a> <ul><li>Dataset imported into MassIVE from <a href="https://cptac-data-portal.georgetown.edu/study-summary/S060">https://cptac-data-portal.georgetown.edu/study-summary/S060</a> on 06/05/21</li></ul>

Dataset Information

Proteogenomic Landscape of Breast Cancer Tumorigenesis and Targeted Therapy.

Publications

Proteogenomic Landscape of Breast Cancer Tumorigenesis and Targeted Therapy.

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