Comprehensive Genomic Studies Emerging Regulatory, Strategic, and Quality Assurance Challenges for Biorepositories
Laboratory for Translational Pathology, Dept of Pathology and Immunology, Washington University School of Medicine, 660 Euclid Ave, Box 8118, St Louis, MO 63110, USA. American Journal of Clinical Pathology
(Impact Factor: 2.51).
07/2012; 138(1):31-41. DOI: 10.1309/AJCPXBA69LNSCVMH
As part of the molecular revolution sweeping medicine, comprehensive genomic studies are adding powerful dimensions to medical research. However, their power exposes new regulatory, strategic, and quality assurance challenges for biorepositories. A key issue is that unlike other research techniques commonly applied to banked specimens, nucleic acid sequencing, if sufficiently extensive, yields data that could identify a patient. This evolving paradigm renders the concepts of anonymized and anonymous specimens increasingly outdated. The challenges for biorepositories in this new era include refined consent processes and wording, selection and use of legacy specimens, quality assurance procedures, institutional documentation, data sharing, and interaction with institutional review boards. Given current trends, biorepositories should consider these issues now, even if they are not currently experiencing sample requests for genomic analysis. We summarize our current experiences and best practices at Washington University Medical School, St Louis, MO, our perceptions of emerging trends, and recommendations.
Available from: sciencedirect.com
[Show abstract] [Hide abstract]
ABSTRACT: Next-generation sequencing (NGS) has emerged as a powerful technique for the detection of genetic variants in the clinical laboratory. NGS can be performed using DNA from FFPE tissue, but it is unknown whether such specimens are truly equivalent to unfixed tissue for NGS applications. To address this question, we performed hybridization-capture enrichment and multiplexed Illumina NGS for 27 cancer-related genes using DNA from 16 paired fresh-frozen and routine FFPE lung adenocarcinoma specimens and conducted extensive comparisons between the sequence data from each sample type. This analysis revealed small but detectable differences between FFPE and frozen samples. Compared with frozen samples, NGS data from FFPE samples had smaller library insert sizes, greater coverage variability, and an increase in C to T transitions that is most pronounced at CpG dinucleotides, suggesting interplay between DNA methylation and formalin-induced changes; however, the error rate, library complexity, enrichment performance, and coverage statistics were not significantly different. Comparison of base calls between paired samples demonstrated concordances of >99.99%, with 96.8% agreement in the single-nucleotide variants detected and >98% accuracy of NGS data when compared with genotypes from an orthogonal single-nucleotide polymorphism array platform. This study demonstrates that routine processing of FFPE samples has a detectable but negligible effect on NGS data and that these samples can be a reliable substrate for clinical NGS testing.
The Journal of molecular diagnostics: JMD 06/2013; 15(5). DOI:10.1016/j.jmoldx.2013.05.004 · 4.85 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: Next generation sequencing (NGS) allows the rapid analysis of genomes and has brought invaluable information on cancer biology and drug targets. Laboratories have started to provide NGS data to physicians to aid in the prescription of targeted drugs. The review presents the recent clinical experience with NGS.
Clinical studies support the potential of NGS to tailor the treatment of patients to alterations in their cancer genome in a process called precision medicine. Case reports, analyses of early phase trials, and series of lung cancer patients have recently shown superior outcome for the matching of drug to specific molecular alterations. NGS is also useful to detect germline mutations associated with hereditary cancers.
NGS and other molecular technologies are transforming the practice of medical oncology and clinical research. Sequencing of primary tumors, metastases, or blood-derived circulating tumor DNA has great potential to guide individualized cancer treatment. However, the integration of NGS as a breakthrough technology is associated with operational challenges such as information processing, medical education and interpretation, and reimbursement.
Current opinion in oncology 04/2014; 26(3). DOI:10.1097/CCO.0000000000000078 · 4.47 Impact Factor
Available from: Michael R Rossi
[Show abstract] [Hide abstract]
ABSTRACT: We describe open, reproducible pipelines that create an integrated genomic
profile of a cancer and use the profile to find mutations associated with disease
and potentially useful drugs. These pipelines analyze high-throughput cancer
exome and transcriptome sequence data together with public databases to find
relevant mutations and drugs. The three pipelines that we have developed are:
(1) an exome analysis pipeline, which uses whole or targeted tumor exome
sequence data to produce a list of putative variants (no matched normal data
are needed); (2) a transcriptome analysis pipeline that processes whole tumor
transcriptome sequence (RNA-seq) data to compute gene expression and find
potential gene fusions; and (3) an integrated variant analysis pipeline that uses
the tumor variants from the exome pipeline and tumor gene expression from
the transcriptome pipeline to identify deleterious and druggable mutations in
all genes and in highly expressed genes. These pipelines are integrated into the
popular Web platform Galaxy at http://usegalaxy.org/cancer to make them
accessible and reproducible, thereby providing an approach for doing standardized,
distributed analyses in clinical studies. We have used our pipeline to identify
similarities and differences between pancreatic adenocarcinoma cancer cell
lines and primary tumors.
Cancer Medicine 01/2015; 4(3). DOI:10.1002/cam4.360 · 2.50 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.