Assessing inter-component heterogeneity of biphasic uterine carcinosarcomas

Yihua Liu, Zachary Weber, F. Anthony San Lucas, Aditya Deshpande, Yasminka A. Jakubek, Raed Sulaiman, Mary Fagerness, Natasha Flier, Joseph Sulaiman, Christel M. Davis, Jerry Fowler, David Starks, Luis Rojas-Espaillat, Alexander J. Lazar, Gareth E. Davies, Erik A. Ehli, Paul Scheet

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Objective: Uterine carcinosarcoma (UCS) is a rare and aggressive form of uterine cancer. It is bi-phasic, exhibiting histological features of both malignant epithelial (carcinoma) and mesenchymal (sarcoma) elements, reflected in ambiguity in accepted treatment guidelines. We sought to study the genomic and transcriptomic profiles of these elements individually to gain further insights into the development of these tumors. Methods: We macro-dissected carcinomatous, sarcomatous, and normal tissues from formalin fixed paraffin embedded uterine samples of 10 UCS patients. Single nucleotide polymorphism microarrays, targeted DNA sequencing and whole-transcriptome RNA-sequencing were performed. Somatic chromosomal alterations (SCAs), point mutation and gene expression profiles were compared between carcinomatous and sarcomatous components. Results: In addition to TP53, other recurrently mutated genes harboring putative driver or loss-of-function mutations included PTEN, FBXW7, FGFR2, KRAS, PIK3CA and CTNNB1, genes known to be involved in UCS. Intra-patient somatic mutation and SCA profiles were highly similar between paired carcinoma and sarcoma samples. An epithelial-mesenchymal transition (EMT) signature tended to differentiate components, with EMT-like status more common in advanced-stage patients exhibiting higher inter-component SCA heterogeneity. Conclusions: From DNA analysis, our results indicate a monoclonal disease origin for this cohort. Yet expression-derived EMT statuses of the carcinomatous and sarcomatous components were often discrepant, and advanced cases displayed greater genomic heterogeneity. Therefore, separately-profiled components of UCS tumors may better inform disease progression or potential.

Original languageEnglish
Pages (from-to)243-249
Number of pages7
JournalGynecologic Oncology
Volume151
Issue number2
DOIs
StatePublished - Nov 2018

Bibliographical note

Funding Information:
The authors wish to acknowledge NIH grants P30 CA016672 and R01 HG005859 .

Publisher Copyright:
© 2018 Elsevier Inc.

Keywords

  • Biphasic
  • Carcinosarcoma
  • Genomics
  • Haplotype
  • Heterogeneity
  • Uterine cancer

ASJC Scopus subject areas

  • Oncology
  • Obstetrics and Gynecology

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