@article{86f642f231494f009e9592681d21b755,
title = "Quantitative analysis of tyrosine phosphorylation from FFPE tissues reveals patient-specific signaling networks",
abstract = "Human tissue samples commonly preserved as formalin-fixed paraffin-embedded (FFPE) tissues after diagnostic or surgical procedures in the clinic represent an invaluable source of clinical specimens for in-depth characterization of signaling networks to assess therapeutic options. Tyrosine phosphorylation (pTyr) plays a fundamental role in cellular processes and is commonly dysregulated in cancer but has not been studied to date in FFPE samples. In addition, pTyr analysis that may otherwise inform therapeutic interventions for patients has been limited by the requirement for large amounts of frozen tissue. Here we describe a method for highly sensitive, quantitative analysis of pTyr signaling networks, with hundreds of sites quantified from one to two 10-mm sections of FFPE tissue specimens. A combination of optimized magnetic bead–based sample processing, optimized pTyr enrichment strategies, and tandem mass tag multiplexing enabled in-depth coverage of pTyr signaling networks from small amounts of input material. Phosphotyrosine profiles of flash-frozen and FFPE tissues derived from the same tumors suggested that FFPE tissues preserve pTyr signaling characteristics in patient-derived xenografts and archived clinical specimens. pTyr analysis of FFPE tissue sections from breast cancer tumors as well as lung cancer tumors highlighted patient-specific oncogenic driving kinases, indicating potential targeted therapies for each patient. These data suggest the capability for direct translational insight from pTyr analysis of small amounts of FFPE tumor tissue specimens.",
author = "Kohale, {Ishwar N.} and Burgenske, {Danielle M.} and Mladek, {Ann C.} and Bakken, {Katrina K.} and Jenevieve Kuang and Boughey, {Judy C.} and Liewei Wang and Carter, {Jodi M.} and Haura, {Eric B.} and Goetz, {Matthew P.} and Sarkaria, {Jann N.} and White, {Forest M.}",
note = "Funding Information: The authors thank members of the White lab for helpful suggestions and the Koch Institute{\textquoteright}s Robert A. Swanson (1969) Biotechnology Center for technical support, specifically the Hope Babette Tang (1983) Histology Facility and the Biopolymers & Proteomics Core Facility. This research was supported by funding from MIT Center for Precision Cancer Medicine; NIH grants U54 CA210180, U01 CA238720, P42 ES027707, and P30 CA14051; and a Koch Institute - Mayo Clinic Cancer Solutions Team Grant. This research was funded in part by the Mayo Clinic Breast Cancer Specialized Program of Research Excellence Grant (P50CA 116201 to M.P. Goetz, J.M. Carter, and L. Wang) and the George M. Eisenberg Foundation for Charities (to M.P. Goetz, L. Wang, and J.C. Boughey). Funding Information: I.N. Kohale reports grants from NIH during the conduct of the study. J. Kuang reports grants from NIH during the conduct of the study. J.C. Boughey reports grants from NIH and foundations during the conduct of the study, as well as grants from Lilly outside the submitted work. E.B. Haura reports grants from NCI during the conduct of the study; grants and personal fees from Revolution Medicines, personal fees and non-financial support from Janssen, and personal fees from Amgen outside the submitted work; and a patent for Protein–Protein Interactions as Cancer Biomarkers issued to Moffitt. M.P. Goetz reports other support from Eagle Pharmaceuticals, Lilly, Biovica, Novartis, Sermonix, Context Therapeutics, Pfizer, Biotheranostics, and AstraZeneca and grants from Pfizer, Sermonix, and Lilly outside the submitted work. J.N. Sarkaria reports grants from Basilea, GlaxoSmithKline, Bristol Myers Squibb, Curtana, Forma, AbbVie, Boehringer Ingelheim, Bayer, Celgene, Cible, Wayshine, Boston Scientific, AstraZeneca, Black Diamond, Karyopharm, and Actuate outside the submitted work. No disclosures were reported by the other authors. Publisher Copyright: {\textcopyright} 2021 American Association for Cancer Research Inc.. All rights reserved.",
year = "2021",
month = jul,
day = "15",
doi = "10.1158/0008-5472.CAN-21-0214",
language = "English (US)",
volume = "81",
pages = "3930--3941",
journal = "Cancer Research",
issn = "0008-5472",
number = "14",
}