MassIVE MSV000087566

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Microscaled Proteogenomic Methods for Precision Oncology

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Description

Shankha Satpathy, Eric J. Jaehnig, et al., Nature Communications volume 11, Article number: 532 (2020)

Cancer proteogenomics promises new insights into cancer biology and treatment efficacy by integrating genomics, transcriptomics and protein profiling including modifications by mass spectrometry (MS). A critical limitation is sample input requirements that exceed many sources of clinically important material. Here we report a proteogenomics approach for core biopsies using tissue-sparing specimen processing and microscaled proteomics. As a demonstration, we analyze core needle biopsies from ERBB2 positive breast cancers before and 48-72 h after initiating neoadjuvant trastuzumab-based chemotherapy. We show greater suppression of ERBB2 protein and both ERBB2 and mTOR target phosphosite levels in cases associated with pathological complete response, and identify potential causes of treatment resistance including the absence of ERBB2 amplification, insufficient ERBB2 activity for therapeutic sensitivity despite ERBB2 amplification, and candidate resistance mechanisms including androgen receptor signaling, mucin overexpression and an inactive immune microenvironment. The clinical utility and discovery potential of proteogenomics at biopsy-scale warrants further investigation.

Genomic Data for samples in the Microscaled Proteogenomic Methods Publication are available from the NIH Database of Genotypes and Phenotypes (dbGaP), Study Accession: phs001907.v1.p1, here

[doi:10.25345/C57K0J] [dataset license: Custom User License]

Keywords: CPTAC

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Principal Investigators:
(in alphabetical order) 		Matthew J. Elliis, Lester and Sue Smith Breast Center and Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, United States
Steven A. Carr, Broad Institute of MIT and Harvard, United States
Submitting User: ccms
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