Microscaled proteogenomic methods for precision oncology.

Abstract:

: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.

journal_name

Nat Commun

journal_title

Nature communications

authors

Satpathy S,Jaehnig EJ,Krug K,Kim BJ,Saltzman AB,Chan DW,Holloway KR,Anurag M,Huang C,Singh P,Gao A,Namai N,Dou Y,Wen B,Vasaikar SV,Mutch D,Watson MA,Ma C,Ademuyiwa FO,Rimawi MF,Schiff R,Hoog J,Jacobs S,Malov

doi

10.1038/s41467-020-14381-2

subject

Has Abstract

pub_date

2020-01-27 00:00:00

pages

532

issue

1

issn

2041-1723

pii

10.1038/s41467-020-14381-2

journal_volume

11

pub_type

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