Pathology tissue-quantitative mass spectrometry analysis to profile histone post-translational modification patterns in patient samples

Research output: Contribution to journalArticlepeer-review

Abstract

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 formalinfixed paraffin-embedded (FFPE) samples. In pairwise comparisons, histone extracted from formalin-fixed paraffinembedded 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 formalinfixed paraffin-embedded archives.

Original languageEnglish
Pages (from-to)866-877
Number of pages12
JournalMolecular and Cellular Proteomics
Volume15
Issue number3
DOIs
Publication statusPublished - Mar 1 2016

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Analytical Chemistry

Fingerprint Dive into the research topics of 'Pathology tissue-quantitative mass spectrometry analysis to profile histone post-translational modification patterns in patient samples'. Together they form a unique fingerprint.

Cite this