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Pathology Tissue-quantitative Mass Spectrometry Analysis to Profile Histone
Post-translational Modification Patterns in Patient Samples
#MMPMID26463340
Noberini R
; Uggetti A
; Pruneri G
; Minucci S
; Bonaldi T
Mol Cell Proteomics
2016[Mar]; 15
(3
): 866-77
PMID26463340
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Histone post-translational modifications (hPTMs) generate a complex combinatorial
code that has been implicated with various pathologies, including cancer.
Dissecting such a code in physiological and diseased states may be exploited for
epigenetic biomarker discovery, but hPTM analysis in clinical samples has been
hindered by technical limitations. Here, we developed a method (PAThology tissue
analysis of Histones by Mass Spectrometry - PAT-H-MS) that allows to perform a
comprehensive, unbiased and quantitative MS-analysis of hPTM patterns on
formalin-fixed paraffin-embedded (FFPE) samples. In pairwise comparisons, histone
extracted from formalin-fixed paraffin-embedded tissues showed patterns similar
to fresh frozen samples for 24 differentially modified peptides from histone H3.
In addition, when coupled with a histone-focused version of the super-SILAC
approach, this method allows the accurate quantification of modification changes
among breast cancer patient samples. As an initial application of the PAThology
tissue analysis of Histones by Mass Spectrometry method, we analyzed breast
cancer samples, revealing significant changes in histone H3 methylation patterns
among Luminal A-like and Triple Negative disease subtypes. These results pave the
way for retrospective epigenetic studies that combine the power of MS-based hPTM
analysis with the extensive clinical information associated with formalin-fixed
paraffin-embedded archives.
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