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      Assessing inter-component heterogeneity of biphasic uterine carcinosarcomas

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          Abstract

          <div class="section"> <a class="named-anchor" id="S1"> <!-- named anchor --> </a> <h5 class="section-title" id="d215996e269">Objective:</h5> <p id="P3">Uterine carcinosarcoma (UCS) is a rare and aggressive form of uterine cancer. It is biphasic, 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. </p> </div><div class="section"> <a class="named-anchor" id="S2"> <!-- named anchor --> </a> <h5 class="section-title" id="d215996e274">Methods:</h5> <p id="P4">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. </p> </div><div class="section"> <a class="named-anchor" id="S3"> <!-- named anchor --> </a> <h5 class="section-title" id="d215996e279">Results:</h5> <p id="P5">In addition to <i>TP53</i>, other recurrently mutated genes harboring putative driver or loss-offunction mutations included <i>PTEN</i>, <i>FBXW7</i>, <i>FGFR2</i>, <i>KRAS</i>, <i>PIK3CA</i> and <i>CTNNB1</i>, 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 advancedstage patients exhibiting higher inter-component SCA heterogeneity. </p> </div><div class="section"> <a class="named-anchor" id="S4"> <!-- named anchor --> </a> <h5 class="section-title" id="d215996e306">Conclusions:</h5> <p id="P6">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. </p> </div>

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          Author and article information

          Journal
          Gynecologic Oncology
          Gynecologic Oncology
          Elsevier BV
          00908258
          November 2018
          November 2018
          : 151
          : 2
          : 243-249
          Article
          10.1016/j.ygyno.2018.08.043
          6214727
          30194005
          0b55233d-4d8d-4814-a2c0-d8162da49e2d
          © 2018

          https://www.elsevier.com/tdm/userlicense/1.0/


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