RNA sequencing of esophageal adenocarcinomas identifies novel fusion transcripts, including NPC1-MELK, arising from a complex chromosomal rearrangement.
Background: Studies of chromosomal rearrangements and fusion transcripts have elucidated mechanisms of tumorigenesis and led to targeted cancer therapies. This study was aimed at identifying novel fusion transcripts in esophageal adenocarcinoma (EAC).Methods: To identify new fusion transcripts assoc...
| Publicado en: | Cancer (0008543X) Vol. 123; no. 20; pp. 3916 - 3926 |
|---|---|
| Autores principales: | , , , , , , , , , , |
| Formato: | research tables/charts Journal Article |
| Publicado: |
Wiley-Blackwell
Oct2017
|
| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=125461669&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 125461669 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 0008543X 23I jtl: Cancer (0008543X) issn: 0008543X maglogo: Y pubinfo: dt: Oct2017 vid: 123 iid: 20 pid: 480 pub: Wiley-Blackwell place: Malden, Massachusetts artinfo: ui: 125461669 125461669 NLM28640357 125461669 10.1002/cncr.30837 NLM28640357 125461669 ppf: 3916 ppct: 10 formats: tig: atl: RNA sequencing of esophageal adenocarcinomas identifies novel fusion transcripts, including NPC1-MELK, arising from a complex chromosomal rearrangement. aug: au: Wang, Zhixiong Cheng, Yulan Abraham, John M. Yan, Rong Liu, Xi Chen, Wei Ibrahim, Sariat Schroth, Gary P. Ke, Xiquan He, Yulong Meltzer, Stephen J. affil: Department of Gastrointestinal Surgery, First Affiliated Hospital of Sun Yat‐Sen University, Guangzhou China sug: subj: Adenocarcinoma Proteins Esophageal Neoplasms Genes RNA Metabolism Receptors, Cell Surface Phosphotransferases Membrane Glycoproteins Adult Middle Age Female Sequence Analysis Aged Carrier Proteins Peptide Hydrolases Case Control Studies Cell Line, Tumor Male Calcium Binding Proteins Reverse Transcriptase Polymerase Chain Reaction Transferases Aged, 80 and Over Human Funding Source Adult: 19-44 years Middle Aged: 45-64 years Aged: 65+ years Aged, 80 & over Female Male ab: Background: Studies of chromosomal rearrangements and fusion transcripts have elucidated mechanisms of tumorigenesis and led to targeted cancer therapies. This study was aimed at identifying novel fusion transcripts in esophageal adenocarcinoma (EAC).Methods: To identify new fusion transcripts associated with EAC, targeted RNA sequencing and polymerase chain reaction (PCR) verification were performed in 40 EACs and matched nonmalignant specimens from the same patients. Genomic PCR and Sanger sequencing were performed to find the breakpoint of fusion genes.Results: Five novel in-frame fusion transcripts were identified and verified in 40 EACs and in a validation cohort of 15 additional EACs (55 patients in all): fibroblast growth factor receptor 2 (FGFR2)-GRB2-associated binding protein 2 (GAB2) in 2 of 55 or 3.6%, Niemann-Pick C1 (NPC1)-maternal embryonic leucine zipper kinase (MELK) in 2 of 55 or 3.6%, ubiquitin-specific peptidase 54 (USP54)-calcium/calmodulin dependent protein kinase II γ (CAMK2G) in 2 of 55 or 3.6%, megakaryoblastic leukemia (translocation) 1 (MKL1)-fibulin 1 (FBLN1) in 1 of 55 or 1.8%, and CCR4-NOT transcription complex subunit 2 (CNOT2)-chromosome 12 open reading frame 49 (C12orf49) in 1 of 55 or 1.8%. A genomic analysis indicated that NPC1-MELK arose from a complex interchromosomal translocation event involving chromosomes 18, 3, and 9 with 3 rearrangement points, and this was consistent with chromoplexy.Conclusions: These data indicate that fusion transcripts occur at a stable frequency in EAC. Furthermore, our results indicate that chromoplexy is an underlying mechanism that generates fusion transcripts in EAC. These and other fusion transcripts merit further study as diagnostic markers and potential therapeutic targets in EAC. Cancer 2017;123:3916-24. © 2017 American Cancer Society. pubtype: Academic Journal doctype: research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
|---|