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Molecular variations in uterine carcinosarcomas identify therapeutic opportunities
  1. Erin Crane1,
  2. Wendel Naumann1,
  3. David Tait1,
  4. Robert Higgins1,
  5. Thomas Herzog2 and
  6. Jubilee Brown1
  1. 1Levine Cancer Institution, Charlotte, North Carolina, USA
  2. 2University of Cincinnati, Cincinnati, Ohio, USA
  1. Correspondence to Dr Erin Crane, Levine Cancer Institution, Charlotte, NC 28209, USA; erin.crane{at}


Objective To perform comprehensive genomic profiling on a large cohort of patients with uterine carcinosarcomas to identify potential therapeutic targets.

Methods Molecular profiling was conducted on 168 retrospectively de-identified patients with uterine carcinosarcomas using the Caris Life Sciences platform. Specimens were evaluated for aberrations in protein expression by immunohistochemistry, DNA sequence mutation using a 592-gene next generation sequencing panel, copy number amplification using next generation sequencing or in situ hybridization, and fusion events using NextGen RNA sequencing. Tumor mutational load and microsatellite instability were also evaluated.

Results We identified 168 patients with uterine carcinosarcoma; median age of the cohort was 67 years. The most common mutations were observed in the following genes: TP53 (86%), PIK3CA (34%), FBXW7 (23%), PTEN (18%), KRAS (16%), PPP2R1A (10%). Tumor mutational load was low to moderate in most cases (50% and 45%, respectively). HER2/neu (ERBB2) was amplified in 9% of tumors. Immunohistochemistry protein expression was elevated in TOP2A (95%), TS (80%), PTEN (76%), and TUBB3 (66%). Mismatch repair deficiency was rare (4%).

Conclusions Multiple somatic mutations and copy number alterations in genes that are therapeutic targets were identified in half of cases. Uterine carcinosarcomas represent an aggressive histology with limited treatment options and poor outcomes, and clinical trials are needed to validate new therapeutic targets.

  • uterine cancer
  • carcinosarcoma

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  • Contributors EC contributed to manuscript conception, data collection, data analysis and interpretation, drafting and revising the article, and final approval of the manuscript. WN, DT, RH, TH, and JB contributed to manuscript conception, critical revision of the article and final approval of the manuscript.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval This retrospective analysis utilized previously collected de-identified data created under the Caris Honest Broker policy and followed consultation with the Western Institutional Review Board, which is the institutional review board of record for Caris Life Sciences. The project was deemed exempt from Institutional Review Board oversight.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data may be obtained from a third party and are not publicly available. All data relevant to the study are included in the article or uploaded as supplementary information. All data relevant to the study are included in the article. Any additional information may be requested by contacting Mary Baker, the Director of Clinical Research Operations, at Caris Life Sciences, 4610 South 44th Place, Phoenix, AZ 85040.