title: Read-through transcripts in normal human lung parenchyma are down-regulated in lung adenocarcinoma.
abstract: Read-through transcripts result from the continuous transcription of adjacent, similarly oriented genes, with the splicing out of the intergenic region. They have been found in several neoplastic and normal tissues, but their pathophysiological significance is unclear. We used high-throughput sequencing of cDNA fragments (RNA-Seq) to identify read-through transcripts in the non-involved lung tissue of 64 surgically treated lung adenocarcinoma patients. A total of 52 distinct read-through species was identified, with 24 patients having at least one read-through event, up to a maximum of 17 such transcripts in one patient. Sanger sequencing validated 28 of these transcripts and identified an additional 15, for a total of 43 distinct read-through events involving 35 gene pairs. Expression levels of 10 validated read-through transcripts were measured by quantitative PCR in pairs of matched non-involved lung tissue and lung adenocarcinoma tissue from 45 patients. Higher expression levels were observed in normal lung tissue than in the tumor counterpart, with median relative quantification ratios between normal and tumor varying from 1.90 to 7.78; the difference was statistically significant (P < 0.001, Wilcoxon's signed-rank test for paired samples) for eight transcripts: ELAVL1-TIMM44, FAM162B-ZUFSP, IFNAR2-IL10RB, INMT-FAM188B, KIAA1841-C2orf74, NFATC3-PLA2G15, SIRPB1-SIRPD, and SHANK3-ACR. This report documents the presence of read-through transcripts in apparently normal lung tissue, with inter-individual differences in patterns and abundance. It also shows their down-regulation in tumors, suggesting that these chimeric transcripts may function as tumor suppressors in lung tissue.
authors.affiliation: Department of Predictive and Prevention Medicine, Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Pintarelli
authors.affiliation: Department of Predictive and Prevention Medicine, Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Alice
authors.initials: A
authors.lastname: Dassano
authors.affiliation: Department of Predictive and Prevention Medicine, Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, Italy.|Present Address: UCD School of Biomolecular and Biomedical Science, University College Dublin, Belfield, Dublin, Ireland.
authors.forename: Chiara E
authors.initials: CE
authors.lastname: Cotroneo
authors.affiliation: Formerly, Department of Predictive and Prevention Medicine, Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Galvan
authors.affiliation: Department of Predictive and Prevention Medicine, Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Noci
authors.affiliation: Department of Health Sciences, University of Milano-Bicocca, Monza, Italy.|Hematology and Clinical Research Unit, San Gerardo Hospital, Monza, Italy.
authors.forename: Rocco
authors.initials: R
authors.lastname: Piazza
authors.affiliation: Department of Health Sciences, University of Milano-Bicocca, Monza, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Pirola
authors.affiliation: Formerly, Department of Health Sciences, University of Milano-Bicocca, Monza, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Spinelli
authors.affiliation: Department of Surgery, San Giuseppe Hospital, Multimedica, Milan, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Incarbone
authors.affiliation: Department of Surgery, IRCCS Fondazione Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Palleschi
authors.affiliation: Department of Surgery, IRCCS Fondazione Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Rosso
authors.affiliation: Department of Surgery, IRCCS Fondazione Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Santambrogio
authors.affiliation: Department of Predictive and Prevention Medicine, Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Tommaso A
authors.initials: TA
authors.lastname: Dragani
authors.affiliation: Department of Predictive and Prevention Medicine, Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Colombo
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D000077192:Adenocarcinoma of Lung; D000368:Aged; D018076:DNA, Complementary / Q000235:genetics; D015536:Down-Regulation; D005260:Female; D020869:Gene Expression Profiling; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008168:Lung / Q000473:pathology*; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D050506:Mutant Chimeric Proteins / Q000235:genetics*; D011013:Pneumonectomy; D012313:RNA / Q000235:genetics; D012326:RNA Splicing; D060888:Real-Time Polymerase Chain Reaction; D017423:Sequence Analysis, RNA; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D018076:DNA, Complementary; D050506:Mutant Chimeric Proteins; D025521:Tumor Suppressor Proteins; D012313:RNA
keywords: RNA-Seq; conjoined genes; gene fusion; lung adenocarcinoma; read-through transcripts