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Table 1 Pathological epigenetic aberrations investigated by epi-proteomics

From: Investigating pathological epigenetic aberrations by epi-proteomics

Disease

Type of sample1

Main findings of MS experiment

Technical improvement

MS method2

Quantification approach 3

Ref

Multiple cancers

Fresh frozen tissue

Loss of H4K20me3 and H4K16ac is a common hallmark of cancer

 

LC–MS, DDA

Label-free

[9]

FFPE, resh/OCT-frozen tissue

Loss of H3K14ac is a common hallmark of cancer, additional tumor- and subtype-specific changes exist

 

LC–MS, DDA

Super-SILAC

[10]

Breast cancer

Fresh frozen, FFPE tissue

Breast cancer subtypes show different histone H3 marks

First protocol to analyze histone PTMs from FFPE tissues

LC–MS, DDA

Super-SILAC

[49]

Fresh frozen, FFPE tissue

Breast cancer subtypes show different histone H4 marks

Improvement in digestion approaches for the analysis of histone H4 PTMs

LC–MS, DDA

Super-SILAC

[51]

Fresh frozen, FFPE tissue (LMD)

Breast cancer subtypes show different histone H3 marks

Analysis of histone PTMs from 500,000 laser microdissected cells

LC–MS, DDA

Super-SILAC

[45]

Fresh frozen, FFPE tissue (LMD)

Differences in histone PTM patters in heterogeneous tumor areas, and in lymphocytes inside/outside the tumor

Analysis of histone PTMs from 1000 laser microdissected cells

LC–MS, DDA

Super-SILAC

[46]

Fresh frozen, FFPE, OCT (LMD)

Lower levels of histone H1 variants in triple-negative breast cancer samples with worse prognosis

Label-free method to quantitate histone H1 variants from low-abundance clinical samples

LC–MS, DDA

Label-free

[84]

Acute myeloid leukemia (AML)

Frozen primary cells

Differences in H3K9me3 in acute myeloid leukemia patient cells

Targeted analysis of 61 histone PTMs from 1000 primary human cells

LC–MS, targeted

Label-free

[47]

Malignant peripheral nerve sheath tumor

FFPE tissue

Loss of PRC2 results in increased levels of H3K27Ac and H3K36me2 and global loss of H3K27me2/3

 

LC–MS, DDA/DIA

Label-free

[50]

Cancer

Frozen serum

Detection of histones from circulating nucleosomes by MS

Development of an enrichment method to isolate circulating nucleosomes

LC–MS, DDA

Label-free

[53]

Colorectal cancer

Frozen plasma

Upregulation of several histone PTMs in the plasma of CRC patients

Development of an enrichment method to isolate circulating nucleosomes

LC–MS, DDA

Heavy spike-in peptides

[52]

Hepatocellular carcinoma

Fresh frozen tissue

H4K20me2 and H4K16ac are biomarkers of microvascular invasion in hepatocellular carcinoma

 

MALDI-IMS

Label-free

[98]

Pediatric brain cancers

FFPE tissue

The missense histone mutation K27M causes changes in H3K36 methylation

 

LC–MS, DDA

Label-free

[90]

Neurologic dysfunction

Primary lymphoblasts and fibroblasts

Aberrant histone PTM patters in patients with germline mutations in genes encoding for histone H3.3 with progressive neurologic dysfunction and congenital anomalies

 

LC–MS, DIA

Label-free

[91]

Alzheimer's disease (AD)

Fresh frozen temporal lobe

Increase in H3K27ac and H3K9ac in AD patients

First integrated multi-OMICs approach including MS-based analysis of histone PTMs

LC–MS, DIA

Label-free

[16]

Fresh frozen temporal lobe

Decrease in histone acetylation in AD patients

SRM method to analyze histone PTMs

LC–MS, DDA, SRM

TMT

[106]

Fresh frozen frontal cortex

Changes in several histone PTMs in AD patients

MRM method to analyze histone PTMs

LC–MS, DDA, MRM

Label-free

[107]

Septic shock

Frozen plasma

H3 and H2B are elevated in septic shock patient sera

 

LC–MS, MRM

Heavy spike-in peptides

[55]

  1. 1FFPE: formalin-fixed paraffin-embedded; OCT: optimal cutting temperature; LMD: laser microdissection. 2LC-MS: liquid chromatography–mass spectrometry; DDA: data-dependent acquisition; DIA: data-independent acquisition; MALDI-IMS: matrix-assisted laser desorption/ionization-imaging; SRM: single reaction monitoring; MRM: multiple reaction monitoring. 3 Stable isotope labeling by amino acids in cell culture; TMT: tandem mass tag. Ref: reference