{
  "id": 5463563,
  "title": "Multi-hit STAG2 mutations define a high-risk subset of MDS and reveal convergent evolutionary targeting of cohesin",
  "url": "https://urgent.news/2026/09/03/multi-hit-stag2-mutations-define-a-high-risk-subset-of-mds-and-reveal",
  "topic": "science",
  "section": "Science",
  "published": "2026-09-03T00:00:00.000Z",
  "source": {
    "name": "bioRxiv",
    "slug": "biorxiv",
    "url": "https://www.biorxiv.org/content/10.64898/2026.09.02.749005v1?rss=1"
  },
  "original_language": "en",
  "account": "A recent study examines the impact of multiple mutations in the STAG2 gene, a cohesin suppressor implicated in myeloid neoplasms. The analysis of 1,967 adult patients revealed that 12% had STAG2 mutations, with 16% experiencing multiple hits. These multi-hit cases exhibited more severe multilineage dysplasia and had a poorer prognosis, particularly among those with myelodysplastic syndromes (MDS). Long-read sequencing in representative cases revealed that distinct truncating STAG2 mutations emerged independently, rather than through a stepwise inactivation process. Furthermore, the variant allele frequency patterns suggested that STAG2 was targeted repeatedly in related clonal populations, indicating convergent evolutionary targeting. Overall, the findings suggest that multi-hit STAG2 mutations are the result of convergent evolution and represent a biologically distinct, adverse-risk subset of MDS.",
  "summary": "STAG2 is the most frequently mutated cohesin gene in myeloid neoplasms, yet the significance of multiple mutations within this X-linked tumor suppressor remains unknown. We analyzed a cohort of 1,967 adult patients with myeloid neoplasms and identified 233 cases (12%) harboring STAG2 mutations, including 38 cases (16%) with multiple STAG2 hits. Patients with multi-hit STAG2 mutations exhibited…",
  "key_points": [],
  "editors_take": null,
  "illustration": null,
  "coverage": {
    "outlets": 1,
    "also_reported_by": []
  },
  "ai_generated": true,
  "disclaimer": "Summaries, key points and the editor’s take are written by software from other outlets’ reporting and may contain errors — always check the linked original."
}