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Howitt BE, Sholl LM, Dal Cin P, Jia Y, Yuan L, MacConaill L, Lindeman N, Kuo F, Garcia E, Nucci MR, Quade BJ. Targeted genomic analysis of Müllerian adenosarcoma. J Pathol. 2015;235(1):37-49. PMID 25231023

One-paragraph summary

Twenty samples from 18 subjects (12 without sarcomatous overgrowth, 6 with; two patients contributed paired typical and SO areas) sequenced on a 275-gene exon panel plus 91 introns for rearrangements. Mean mutation count did not differ with versus without SO (9.7 vs 9.6). Mean gene-level CNVs did (24.6 vs 5, p=0.0002). Recurrent events: MDM2/CDK4 amplification 5/18 (28%) with accompanying IHC; MYBL1 amplification 4/18 (22%), predominantly in SO; PIK3CA/AKT/PTEN pathway 13/18 (72%); TP53 mutation in only two cases, both with SO; ATRX mutation in 3/18, all SO-associated; no rearrangements. SO is described as “the only established histological variable associated with higher stage and shorter survival.” Specific molecular or IHC diagnostic tools were lacking.

Key findings

  • SO tracks copy-number complexity, not mutation burden.
  • MDM2/CDK4 co-amplification in 28%.
  • PI3K pathway alteration in 72%; no PI3K-selected adenosarcoma trial was identified in the 2026-09-01 registry search.
  • No rearrangement was identified on this panel; later work reported recurrent ESR1 fusions in an adenosarcoma-like subset (Agaimy 2026, PMID 41555057), with classification still unresolved.

Limitations

  • n=18 subjects, targeted panel not whole genome/exome.
  • Two paired samples: limited intra-tumour evolution data.
  • No outcome analysis of the molecular groups (the clinical claim about SO is cited, not re-estimated).

Why it matters

This is the genomic baseline every later sequencing paper (Hodgson, Geyer, Momeni Boroujeni, Chapel, Agaimy) is in conversation with. A PubMed search rerun 2026-09-01 found no prospectively validated diagnostic molecular test; Agaimy’s fusion series is a 12-case classification study, not assay validation (PMID 41555057).

Cited by wiki pages

  • overview
  • pathology-and-diagnosis
  • sarcomatous-overgrowth
  • molecular-and-genomic-features
  • clinical-trials-landscape