Tumor transcriptome sequencing reveals allelic expression imbalances associated with copy number alterations

Brian B. Tuch, Rebecca R. Laborde, Xing Xu, Jian Gu, Christina B. Chung, Cinna K. Monighetti, Sarah J. Stanley, Kerry D. Olsen, Jan L. Kasperbauer, Eric J. Moore, Adam J. Broomer, Ruoying Tan, Pius M. Brzoska, Matthew W. Muller, Asim S. Siddiqui, Yan W. Asmann, Yongming Sun, Scott Kuersten, Melissa A. Barker, Francisco M. De La VegaDavid I. Smith

Research output: Contribution to journalArticlepeer-review

98 Scopus citations


Due to growing throughput and shrinking cost, massively parallel sequencing is rapidly becoming an attractive alternative to microarrays for the genome-wide study of gene expression and copy number alterations in primary tumors. The sequencing of transcripts (RNA-Seq) should offer several advantages over microarray-based methods, including the ability to detect somatic mutations and accurately measure allele-specific expression. To investigate these advantages we have applied a novel, strand-specific RNA-Seq method to tumors and matched normal tissue from three patients with oral squamous cell carcinomas. Additionally, to better understand the genomic determinants of the gene expression changes observed, we have sequenced the tumor and normal genomes of one of these patients. We demonstrate here that our RNA-Seq method accurately measures allelic imbalance and that measurement on the genome-wide scale yields novel insights into cancer etiology. As expected, the set of genes differentially expressed in the tumors is enriched for cell adhesion and differentiation functions, but, unexpectedly, the set of allelically imbalanced genes is also enriched for these same cancer-related functions. By comparing the transcriptomic perturbations observed in one patient to his underlying normal and tumor genomes, we find that allelic imbalance in the tumor is associated with copy number mutations and that copy number mutations are, in turn, strongly associated with changes in transcript abundance. These results support a model in which allele-specific deletions and duplications drive allele-specific changes in gene expression in the developing tumor.

Original languageEnglish (US)
Article numbere9317
JournalPloS one
Issue number2
StatePublished - Feb 19 2010

ASJC Scopus subject areas

  • General


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