Transcriptome sequencing in Sézary syndrome identifies Sézary cell and mycosis fungoides-associated IncRNAs and novel transcripts

Carolyn S. Lee, Alexander Ungewickell, Aparna Bhaduri, Kun Qu, Dan E. Webster, Randall Armstrong, Wen Kai Weng, Cody J. Aros, Angela Mah, Richard O. Chen, Meihong Lin, Uma Sundram, Howard Y. Chang, Markus Kretz, Youn H. Kim, Paul A. Khavari

Research output: Contribution to journalArticlepeer-review

65 Scopus citations

Abstract

Sézary syndrome (SS) is an aggressive cutaneous T-cell lymphoma (CTCL) of unknown etiology in which malignant cells circulate in the peripheral blood. To identify viral elements, gene fusions, and gene expression patterns associated with this lymphoma, flow cytometry was used to obtain matched pure populations of malignant Sézary cells (SCs) versus nonmalignant CD4+ T cells from 3 patients for whole transcriptome, paired-end sequencing with an average depth of 112 million reads per sample. Pathway analysis of differentially expressed genes identified mis-regulation of PI3K/Akt, TGFβ, and NF-κB pathways as well as T-cell receptor signaling. Bioinformatic analysis did not detect either nonhuman transcripts to support a viral etiology of SS or recurrently expressed gene fusions, but it did identify 21 SC-associated annotated long noncoding RNAs (IncRNAs). Transcriptome assembly by multiple algorithms identified 13 differentially expressed unannotated transcripts termed Sézary cell-associated transcripts (SeCATs) that include 12 predicted IncRNAs and a novel transcript with coding potential. Highthroughput sequencing targeting the 3' end of polyadenylated transcripts in archived tumors from 24 additional patients with tumor-stage CTCL confirmed the differential expression of SC-associated IncRNAs and SeCATs in CTCL. Our findings characterize the SS transcriptome and support recent reports that implicate IncRNA dysregulation in human malignancies.

Original languageEnglish (US)
Pages (from-to)3288-3297
Number of pages10
JournalBlood
Volume120
Issue number16
DOIs
StatePublished - Oct 18 2012
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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