Uterine Leiomyoma (ULM)

Overview

Uterine leiomyoma (fibroid) is the most common benign uterine neoplasm, classified in OncoTree under Uterine Sarcoma (USMT) despite its benign behaviour. Molecularly, the dominant driver is MED12 exon 2 mutations (70–80% of cases in prior literature). HMGA1/HMGA2 chromosomal rearrangements define a distinct subgroup. Uterine leiomyomas share molecular hallmarks with endometrial polyps, including HMGA1/2 rearrangement patterns and ZMAT3 upregulation, suggesting convergent or related oncogenic mechanisms in benign uterine lesions.

Cohorts in the corpus

  • No dedicated ULM cohort study in the corpus. Referenced as a comparison entity in a genomic study of endometrial polyps (N=23 WGS discovery + 54 FFPE validation) PMID:28445112.

Recurrent alterations

  • MED12 — dominant driver of uterine leiomyomas (70–80%) per prior literature; notably absent as a recurrently mutated driver in the endometrial polyp cohort used as comparator, highlighting molecular differences between ULM and endometrial polyps PMID:28445112.
  • HMGA1 and HMGA2 — chromosomal rearrangements are a recognised secondary driver mechanism in ULM; shared biology with endometrial polyps where HMGA1/2 rearrangements occur in 74% (17/23) of cases via enhancer hijacking (non-fusion mechanism). ZMAT3 upregulation (most upregulated gene in HMGA-aberrant polyps, log2FC 1.65) is also a known ULM biomarker PMID:28445112.
  • PLAG1 — transcriptional target downstream of HMGA1/2 rearrangements; upregulated in HMGA1-rearranged (log2FC 3.22) and HMGA2-rearranged (log2FC 3.38) endometrial polyps, paralleling its role in ULM biology PMID:28445112.
  • ZMAT3 — most upregulated gene in HMGA1/2-aberrant endometrial polyps (q=6.98×10⁻¹³, log2FC 1.65); previously reported as the most upregulated gene in uterine leiomyomas regardless of driver, indicating shared transcriptional consequences of HMGA dysregulation across benign uterine lesions PMID:28445112.

Subtypes

  • MED12-mutant leiomyoma (~70–80%): dominant subtype in prior literature; hotspot exon 2 mutations.
  • HMGA1/HMGA2-rearranged leiomyoma: chromosomal rearrangements with enhancer-hijacking mechanism, shared with endometrial polyps; associated with PLAG1/ZMAT3 overexpression PMID:28445112.

Therapeutic landscape

  • No established targeted therapies for ULM. Authors of PMID:28445112 note that HMGA2 gene silencing has been explored in ovarian carcinoma and could in principle be repurposed across HMGA-driven uterine lesions (ULM and endometrial polyps), but no clinical data in ULM exist in the corpus PMID:28445112.

Sources

  • PMID:28445112 — Reinikka et al.; WGS/RNA-seq of endometrial polyps; ULM discussed as comparator sharing HMGA1/2 and ZMAT3 biology.

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