Long-range transcriptome sequencing reveals cancer cell growth regulatory chimeric mRNA.
Neoplasia
; 14(11): 1087-96, 2012 Nov.
Article
en En
| MEDLINE
| ID: mdl-23226102
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.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
ARN Mensajero
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Proteínas Mutantes Quiméricas
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Transcriptoma
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Neoplasias
Límite:
Humans
Idioma:
En
Año:
2012
Tipo del documento:
Article