Table 1 Key findings from selected studies identifying cohesin mutations in myeloid malignancies
From: Cohesin mutations in myeloid malignancies: underlying mechanisms
Myeloid disorder(s) | Cohesin mutation rate | Rationale and key findings | Ref # |
|---|---|---|---|
AML | 26/200 | 200 de novo AML samples were submitted to whole-genome/exome sequencing. The genes identified as recurrently mutated were grouped into nine functional categories important for AML: the cohesin complex was one such category. Cohesin complex mutations were mutually exclusive. | [20] |
(13%) | |||
AML | 7/108 | Whole-genome sequencing (WGS) of 24 normal-karyotype M1 and M3 AML samples. Cohesin genes were only mutated in M1 samples. Cohesin mutations were mutually exclusive and were not associated with chromosomal instability. | [21] |
(6.5%) | |||
AML | 23/389 | Targeted sequencing of cohesin genes in 389 AML samples. Cohesin mutations significantly co-occurred with NPM1 mutations. Allelic burden analysis suggested cohesin mutations occurred early in AML. | [24] |
(5.9%) | |||
AML | 23/197 | Targeted sequencing of 51 myeloid neoplasm candidate genes in 197 AML samples. Cohesin mutations were not associated with overall survival. | [26] |
(11.7%) | |||
AML | 7/170 | Targeted sequencing of AML candidate loci in 50 AML samples. RAD21 mutations were present in all AML subtypes and were significantly associated with RAS mutations. | [27] |
(4.1%) | |||
AML | 12/158 | WGS of eight MDS and subsequent secondary-AML patient genomes. Targeted sequencing of 94 MDS/AML candidate loci. Each clone contained at least one mutation that recurs in MDS/AML. STAG2 mutations significantly co-occurred with RUNX1 mutations. | [28] |
MDS | (7.6%) | ||
MDS | Approximately 15% | Targeted sequencing of 104 MDS/AML candidate genes in 944 MDS samples. 47 genes were recurrently mutated in MDS. 14 of these genes (including STAG2) could successfully predict survival-outcome risk groups. STAG2 and SMC1A mutations were significantly associated with adverse patient outcome. | [29] |
AML | 65/610 | Targeted sequencing of cohesin complex genes was undertaken in a cohort of 610 samples from various myeloid neoplasms. The core components of cohesin were significantly mutated. Cohesin mutations were present in the major tumor population in 15/20 available samples, indicating that cohesin mutations often occur as early events in oncogenesis. | [25] |
MDS | (10.7%) | ||
CMML | |||
CML | |||
MPN | |||
TAM | 39/86 | WGS of the genomes of TAM, AMKL, and DS-AMKL patients. Progression to DS-AMKL required acquisition of further mutations, including RAD21, STAG2, NRAS, CTCF, EZH2, and TP53. | [30] |
AMKL | (45.3%) | ||
DS-AMKL | Cohesin mutations were present at a much higher rate in DS-AMKL than AMKL. Allelic burden analysis suggested that cohesin mutations occurred early in DS-AMKL. |