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] |