Whole-genome and transcriptome profiling of a metastatic thyroid-like follicular renal cell carcinoma

Cold Spring Harb Mol Case Stud. 2018 Dec 17;4(6):a003137. doi: 10.1101/mcs.a003137. Print 2018 Dec.

Abstract

Thyroid-like follicular renal cell carcinoma (TLFRCC) is a rare cancer with few reports of metastatic disease. Little is known regarding genomic characteristics and therapeutic targets. We present the clinical, pathologic, genomic, and transcriptomic analyses of a case of a 27-yr-old male with TLFRCC who presented initially with bone metastases of unknown primary. Genomic DNA from peripheral blood and metastatic tumor samples were sequenced. A transcriptome of 280 million sequence reads was generated from the same tumor sample. Tumor somatic expression profiles were analyzed to detect aberrant expression. Genomic and transcriptomic data sets were integrated to reveal dysregulation in pathways and identify potential therapeutic targets. Integrative genomic analysis with The Cancer Genome Atlas (TCGA) data set revealed the following outliers in gene expression profiles: CDK6 (81st percentile), MYC (99th percentile), AR (100th percentile), PDGFRA and PDGFRB (99th and 100th percentiles, respectively), and MAP2K2 (86th percentile). The patient received first-line sunitinib to target PDGFRA and PDGFRB and had stable disease for >6 mo, followed by nivolumab upon progression. To the authors' knowledge, this is the first reported case of comprehensive somatic genomic analyses in a patient with metastatic TLFRCC. Somatic analyses provided molecular confirmation of the primary site of cancer and potential therapeutic strategies in a rare disease with little evidence of efficacy on systemic therapy.

Keywords: malignant genitourinary tract tumor; renal neoplasm.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma, Follicular / genetics*
  • Adult
  • Biomarkers, Tumor / genetics
  • Carcinoma, Renal Cell / genetics*
  • Gene Expression Profiling / methods
  • Genome
  • Genome-Wide Association Study / methods
  • Genomics
  • Humans
  • Male
  • Mutation
  • Neoplasm Metastasis / genetics
  • Neoplasms / diagnosis
  • Neoplasms / genetics
  • Receptor, Platelet-Derived Growth Factor alpha / genetics
  • Receptor, Platelet-Derived Growth Factor beta / genetics
  • Sunitinib / therapeutic use
  • Transcriptome

Substances

  • Biomarkers, Tumor
  • Receptor, Platelet-Derived Growth Factor alpha
  • Receptor, Platelet-Derived Growth Factor beta
  • Sunitinib

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