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BMC Cancer

, 12:124

First Online: 29 March 2012Received: 04 November 2011Accepted: 29 March 2012DOI: 10.1186-1471-2407-12-124

Cite this article as: Waldron, L., Simpson, P., Parmigiani, G. et al. BMC Cancer 2012 12: 124. doi:10.1186-1471-2407-12-124

Abstract

BackgroundWith over 20 million formalin-fixed, paraffin-embedded FFPE tissue samples archived each year in the United States alone, archival tissues remain a vast and under-utilized resource in the genomic study of cancer. Technologies have recently been introduced for whole-transcriptome amplification and microarray analysis of degraded mRNA fragments from FFPE samples, and studies of these platforms have only recently begun to enter the published literature.

ResultsThe Emerging Technologies for Translational Bioinformatics symposium on gene expression profiling for archival tissues featured presentations of two large-scale FFPE expression profiling studies each involving over 1,000 samples, overviews of several smaller studies, and representatives from three leading companies in the field Illumina, Affymetrix, and NuGEN. The meeting highlighted challenges in the analysis of expression data from archival tissues and strategies being developed to overcome them. In particular, speakers reported higher rates of clinical sample failure from 10% to 70% than are typical for fresh-frozen tissues, as well as more frequent probe failure for individual samples. The symposium program is available at http:-www.hsph.harvard.edu-ffpe.

ConclusionsMultiple solutions now exist for whole-genome expression profiling of FFPE tissues, including both microarray- and sequencing-based platforms. Several studies have reported their successful application, but substantial challenges and risks still exist. Symposium speakers presented novel methodology for analysis of FFPE expression data and suggestions for improving data recovery and quality assessment in pre-analytical stages. Research presentations emphasized the need for careful study design, including the use of pilot studies, replication, and randomization of samples among batches, as well as careful attention to data quality control. Regardless of any limitations in quantitave transcriptomics for FFPE tissues, they are often the only biospecimens available for large patient populations with long-term history and clinical follow-up. Current challenges can be expected to remain as RNA sequencing matures, and they will thus motivate ongoing research efforts into noise reduction and identification of robust, translationally relevant biological signals in expression data from FFPE tissues.

AbbreviationsCtCycle Threshold

qRT-PCRQuantitative Real-time PCR

RINRNA Integrity Number

FFPEFormalin-Fixed Paraffin-Embedded

H and EHematoxylin and Eosin Stain

DSNduplex-specific nuclease

WG-DASLWhole-Genome cDNA-mediated Annealing Selection, extension, and Ligation.

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Autor: Levi Waldron - Peter Simpson - Giovanni Parmigiani - Curtis Huttenhower

Fuente: https://link.springer.com/







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