Clinically available molecular tests to detect common adaptive mutations in patients with inherited bone marrow failure and MDS predisposition syndromes
| Somatic genetic rescue mechanism . | Molecular test . |
|---|---|
| Somatic 2nd site mutations Other direct reversion mutations | Somatic NGS of gene of interest* |
| Indirect rescue mutations such as: TERT promoter** POT1 | Somatic NGS of gene of interest* |
| Clonal cytogenetic abnormalities such as: Interstitial deletion 20q Isochromosome 7q Monosomy 7 | Conventional karyotype FISH |
| Copy neutral-LOH to detect UPD | Chromosomal microarray |
| Somatic genetic rescue mechanism . | Molecular test . |
|---|---|
| Somatic 2nd site mutations Other direct reversion mutations | Somatic NGS of gene of interest* |
| Indirect rescue mutations such as: TERT promoter** POT1 | Somatic NGS of gene of interest* |
| Clonal cytogenetic abnormalities such as: Interstitial deletion 20q Isochromosome 7q Monosomy 7 | Conventional karyotype FISH |
| Copy neutral-LOH to detect UPD | Chromosomal microarray |
Whether the gene of interest is included in clinically available somatic NGS panels is gene dependent. Clinical assays to date also have a higher threshold for detection of somatic mutations than the more sensitive deep sequencing approaches utilized in the research setting.
Somatic genetic rescue mutations at three canonical sites in the TERT promoter are found in patients with short telomere syndromes: c.-124, c.-146 and c.-57. That latter site, c.-57 C>T, is less commonly included in clinical somatic mutation panels.
FISH, fluorescence in situ hybridization.