title: Transcriptome sequencing in Sezary syndrome identifies Sezary cell and mycosis fungoides-associated lncRNAs and novel transcripts.
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 (lncRNAs). Transcriptome assembly by multiple algorithms identified 13 differentially expressed unannotated transcripts termed Sézary cell-associated transcripts (SeCATs) that include 12 predicted lncRNAs and a novel transcript with coding potential. High-throughput 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 lncRNAs and SeCATs in CTCL. Our findings characterize the SS transcriptome and support recent reports that implicate lncRNA dysregulation in human malignancies.
authors.affiliation: Programs in Epithelial Biology, Department of Dermatology, Stanford University, CA, USA.
authors.forename: Carolyn S
authors.initials: CS
authors.lastname: Lee
authors.forename: Alexander
authors.initials: A
authors.lastname: Ungewickell
authors.forename: Aparna
authors.initials: A
authors.lastname: Bhaduri
authors.forename: Kun
authors.initials: K
authors.lastname: Qu
authors.forename: Dan E
authors.initials: DE
authors.lastname: Webster
authors.forename: Randall
authors.initials: R
authors.lastname: Armstrong
authors.forename: Wen-Kai
authors.initials: WK
authors.lastname: Weng
authors.forename: Cody J
authors.initials: CJ
authors.lastname: Aros
authors.forename: Angela
authors.initials: A
authors.lastname: Mah
authors.forename: Richard O
authors.initials: RO
authors.lastname: Chen
authors.forename: Meihong
authors.initials: M
authors.lastname: Lin
authors.forename: Uma
authors.initials: U
authors.lastname: Sundram
authors.forename: Howard Y
authors.initials: HY
authors.lastname: Chang
authors.forename: Markus
authors.initials: M
authors.lastname: Kretz
authors.forename: Youn H
authors.initials: YH
authors.lastname: Kim
authors.forename: Paul A
authors.initials: PA
authors.lastname: Khavari
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D006801:Humans; D009182:Mycosis Fungoides / Q000235:genetics* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D062085:RNA, Long Noncoding / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012751:Sezary Syndrome / Q000235:genetics* / Q000473:pathology; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D062085:RNA, Long Noncoding; D012333:RNA, Messenger