Table 1.
Studies of somatic single-nucleotide variant signatures in the brain in aging and neurodegeneration, along with selected other human tissues
| Study | Tissue/cell | Method | Biological context | Mutational signature(s)a |
|---|---|---|---|---|
| Brain | ||||
| Hoang et al. (51) | Bulk brain (frontal cortex), colon, kidney | Dilution followed by bulk whole-genome sequencing (BotSeqS) | Aging | None identified |
| Park et al. (93) | Bulk brain (hippocampus) | Bulk whole-exome sequencing | Alzheimer’s disease | COSMIC signature SBS18 |
| Lodato et al. (73) | Neurons (prefrontal cortex) | Single-cell whole-genome sequencing | Aging | COSMIC signature 5 |
| DNA repair deficiency neurodegeneration | COSMIC signature 8 | |||
| Other tissues | ||||
| Blokzijl et al. (12) | Adult stem cells of small intestine, colon, liver | Whole-genome sequencing of clonal organoid cultures derived from primary multipotent cells | Aging | COSMIC signature 5 |
| Osorio et al. (90) | Hematopoietic stem cells | Whole-genome sequencing of clonal cultures | Aging | COSMIC signature 5 |
| Franco et al. (37) | Skeletal muscle resident progenitor/stem (satellite) cells | Whole-genome sequencing of in vitro clonally expanded single cells | Aging | COSMIC signatures 1, 5, and 8 |
| Zhang et al. (132) | B lymphocytes | Single-cell whole-genome sequencing | Aging | COSMIC signatures 1 and 5 |
| Lee-Six et al. (70) | Colon (crypts) | Whole-genome sequencing of colorectal crypts, to represent clones from colorectal stem cells | Aging | COSMIC signatures SBS5 and SBS1 |
| Franco et al. (36) | Kidney tubules, epidermis, subcutaneous adipose tissue, visceral adipose tissue | Whole-genome sequencing of in vitro clonally expanded single cells | Aging | COSMIC signatures SBS1, SBS3/8, SBS5, and SBS40 |
a
Catalogue of Somatic Mutations in Cancer (COSMIC) v3 single-base substitution signatures SBS1 and SBS5 are similar and analogous to COSMIC v2 signatures 1 and 5, respectively (126).