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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.

SUBMITTER: Plebani R

PROVIDER: S-EPMC3514740 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature

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Long-range transcriptome sequencing reveals cancer cell growth regulatory chimeric mRNA.

Plebani Roberto R Oliver Gavin R GR Trerotola Marco M Guerra Emanuela E Cantanelli Pamela P Apicella Luana L Emerson Andrew A Albiero Alessandro A Harkin Paul D PD Kennedy Richard D RD Alberti Saverio S

Neoplasia (New York, N.Y.) 20121101 11

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. ...[more]

PMID: 23226102

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Long-range transcriptome sequencing reveals cancer cell growth regulatory chimeric mRNA.

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Long-range transcriptome sequencing reveals cancer cell growth regulatory chimeric mRNA.

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