| _version_ |
1826194255291351040
|
| collection |
MIT
|
| description |
© 2020 The Authors 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.
|
| first_indexed |
2024-09-23T09:53:16Z
|
| format |
Article
|
| id |
mit-1721.1/133609
|
| institution |
Massachusetts Institute of Technology
|
| language |
English
|
| last_indexed |
2024-09-23T09:53:16Z
|
| publishDate |
2021
|
| publisher |
Elsevier BV
|
| record_format |
dspace
|
| spelling |
mit-1721.1/1336092021-10-28T04:39:02Z Proteogenomic Landscape of Breast Cancer Tumorigenesis and Targeted Therapy © 2020 The Authors 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. 2021-10-27T19:53:48Z 2021-10-27T19:53:48Z 2020 2021-09-10T17:45:03Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/133609 en 10.1016/J.CELL.2020.10.036 Cell Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier BV Elsevier
|
| spellingShingle |
Proteogenomic Landscape of Breast Cancer Tumorigenesis and Targeted Therapy
|
| title |
Proteogenomic Landscape of Breast Cancer Tumorigenesis and Targeted Therapy
|
| title_full |
Proteogenomic Landscape of Breast Cancer Tumorigenesis and Targeted Therapy
|
| title_fullStr |
Proteogenomic Landscape of Breast Cancer Tumorigenesis and Targeted Therapy
|
| title_full_unstemmed |
Proteogenomic Landscape of Breast Cancer Tumorigenesis and Targeted Therapy
|
| title_short |
Proteogenomic Landscape of Breast Cancer Tumorigenesis and Targeted Therapy
|
| title_sort |
proteogenomic landscape of breast cancer tumorigenesis and targeted therapy
|
| url |
https://hdl.handle.net/1721.1/133609
|