{
  "abstract": "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 increased multilineage dysplasia compared with single-hit cases and experienced inferior overall survival, an effect driven primarily by patients with myelodysplastic syndromes (MDS). To investigate the molecular basis of recurrent STAG2 acquisition, we performed long-read sequencing in representative cases with phaseable STAG2 mutations. In the informative case examined, distinct truncating STAG2 mutations did not co-occur on the same DNA molecule, supporting independent acquisition rather than stepwise allelic inactivation. Cohort-level variant allele frequency patterns were consistent with recurrent evolutionary targeting of STAG2 across related clonal populations. Together, these findings support a model in which multi-hit STAG2 mutations arise through convergent evolution and define a biologically distinct, adverse-risk subset of MDS.",
  "abstract_shown": true,
  "affiliations": [
    "Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 18,
  "authors": [
    {
      "name": "E.-o. B. Udoh"
    },
    {
      "name": "Y. Chen"
    },
    {
      "name": "M. D'Addona"
    },
    {
      "name": "E. Stewart"
    },
    {
      "name": "R. Deng"
    },
    {
      "name": "F. de Almeida Sartori"
    },
    {
      "name": "S. Unlu"
    },
    {
      "name": "Z. Brady"
    },
    {
      "name": "R. Zhu"
    },
    {
      "name": "X. Cheng"
    },
    {
      "name": "V. Scoca"
    },
    {
      "name": "J. J. Xu"
    },
    {
      "name": "S. Doulatov"
    },
    {
      "name": "K. Theil"
    },
    {
      "name": "D. Bosler"
    },
    {
      "name": "V. Visconte"
    },
    {
      "name": "J. P. Maciejewski"
    },
    {
      "affs": [
        0
      ],
      "name": "A. D. Viny"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/7rh0zfbqedvnq.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.02.749005",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.02.749005v1.full",
  "id": "7rh0zfbqedvnq",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.02.749005v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "cancer biology"
    ],
    [
      "openalex",
      "2720|Acute Myeloid Leukemia Research"
    ]
  ],
  "openalex": "W7207711709",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.02.749005v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-02",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/7rh0zfbqedvnq.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:10Z",
      "native_id": "10.64898/2026.09.02.749005",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.02.749005v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "biorxiv:cancer biology",
      "subfield": "oncology"
    }
  ],
  "title": "Multi-hit STAG2 mutations define a high-risk subset of MDS and reveal convergent evolutionary targeting of cohesin",
  "title_text": "Multi-hit STAG2 mutations define a high-risk subset of MDS and reveal convergent evolutionary targeting of cohesin",
  "type": "preprint",
  "updated_at": "2026-10-30T12:19:10Z",
  "url": "https://research.draconitic.com/paper/7rh0zfbqedvnq",
  "venue": "bioRxiv",
  "versions": []
}