title: Long-range transcriptome sequencing reveals cancer cell growth regulatory chimeric mRNA.
abstract: mRNA chimeras from chromosomal translocations often play a role as transforming oncogenes. However, cancer transcriptomes also contain mRNA chimeras that may play a role in tumor development, which arise as transcriptional or post-transcriptional events. To identify such chimeras, we developed a deterministic screening strategy for long-range sequence analysis. High-throughput, long-read sequencing was then performed on cDNA libraries from major tumor histotypes and corresponding normal tissues. These analyses led to the identification of 378 chimeras, with an unexpectedly high frequency of expression (≈2 x 10(-5) of all mRNA). Functional assays in breast and ovarian cancer cell lines showed that a large fraction of mRNA chimeras regulates cell replication. Strikingly, chimeras were shown to include both positive and negative regulators of cell growth, which functioned as such in a cell-type-specific manner. Replication-controlling chimeras were found to be expressed by most cancers from breast, ovary, colon, uterus, kidney, lung, and stomach, suggesting a widespread role in tumor development.
authors.affiliation: Unit of Cancer Pathology, Centre of Excellence for Research on Aging, G. D'Annunzio University Foundation, Chieti, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Plebani
authors.forename: Gavin R
authors.initials: GR
authors.lastname: Oliver
authors.forename: Marco
authors.initials: M
authors.lastname: Trerotola
authors.forename: Emanuela
authors.initials: E
authors.lastname: Guerra
authors.forename: Pamela
authors.initials: P
authors.lastname: Cantanelli
authors.forename: Luana
authors.initials: L
authors.lastname: Apicella
authors.forename: Andrew
authors.initials: A
authors.lastname: Emerson
authors.forename: Alessandro
authors.initials: A
authors.lastname: Albiero
authors.forename: Paul D
authors.initials: PD
authors.lastname: Harkin
authors.forename: Richard D
authors.initials: RD
authors.lastname: Kennedy
authors.forename: Saverio
authors.initials: S
authors.lastname: Alberti
mesh_terms: D001483:Base Sequence; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008969:Molecular Sequence Data; D050506:Mutant Chimeric Proteins / Q000235:genetics*; D009369:Neoplasms / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*; D016415:Sequence Alignment; D059467:Transcriptome
chemical_list: D050506:Mutant Chimeric Proteins; D012333:RNA, Messenger