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MPI Researchers Explore FFPE Tumor Sequencing


Researchers at the Max Planck Institute for Molecular Genetics in Berlin have shown that they can use next-generation sequencing to analyze DNA from formalin-fixed paraffin-embedded samples stored for as long as 18 years, and that they can detect several types of genetic variation, including copy number alterations and certain SNPs, in FFPE tumor samples.

The ability to sequence FFPE tumor samples would open up large tumor collections from clinical trials for sequence analysis and might help researchers identify genetic alterations that are linked to disease progression or response to cancer therapy. However, sequencing such samples has proven difficult because the formaldehyde compromises the nucleic acids in the tissue.

"The majority of human tumor samples are currently stored as FFPE tumors, so methods to permit the large-scale analysis of such samples will be of great benefit," says Victor Velculescu, director of cancer genetics at the Ludwig Center at Johns Hopkins University. Velculescu was not involved in the study.

FFPE samples, because they are readily available in large numbers from hospital tissue banks, are especially useful for researchers who want to analyze rare tumors, or a subset of patients with certain attributes, for example responders and non-responders to therapy, or patients with advanced disease, according to Michal Schweiger, a group leader in the department of vertebrate genomics at the MPI and the first author of the study, which was published in PLoS One.

They sequenced the samples on an Illumina Genome Analyzer with 36-base or 40-base unpaired reads, generating on the order of 3 million reads per sample, and aligned these reads to the NCBI human reference genome. They found that the number of reads and their distribution across the genome was similar for snap-frozen and FFPE tissues, "proving that fresh FFPE tissues can be used for high-throughput resequencing approaches," according to the study.

— Julia Karow

Sequencing Notes

A workshop held by NHGRI on the future of sequencing led to recommendations that the institute maintain its support for large-scale sequencing centers and provide opportunities for smaller groups to conduct sequencing projects involving next-generation platforms. Participants encouraged NHGRI to work toward better computational resources to analyze and integrate sequence data.

Researchers at the Broad Institute published a proof-of-principle study demonstrating how to fill in some of the sequence gaps in the human genome using Roche 454 sequencing. The paper, which came out in Genome Biology, showed that 454 sequencing could fill in gaps caused by low complexity sequence that is difficult to clone into bacteria.


$43 million

Amount NIAID awarded to the Broad Institute and the J. Craig Venter Institute to provide pathogen sequencing services

Funded Grants

$340,000/FY 2009
Quantifying the Genome-wide Distribution of Transcriptionally-engaged RNA Polymer
Grantee: John Lis, Cornell University
Began: Jan. 24, 2009; Ends: Dec. 31, 2011

This award from NHGRI will be used to "develop a general and highly-sensitive method that maps the position, amount, and orientation of transcriptionally-engaged RNA polymerases across the entire genomes of mammalian cells and Drosophila," according to the abstract. The approach will build on GRO-seq (for global nuclear run-on) to offer a global view of transcription.

$46,826/FY 2009
Novel insight into stability and change in a basal vetebrate genome
Grantee: Jeramiah Smith, Benaroya Research Institute
Began: Apr. 16, 2009; Ends: Apr. 15, 2011

Smith will use the funding to study the sea lamprey, a model system for vertebrate biology that was selected for whole-genome sequencing by NHGRI, and "to elucidate the mechanisms that promote stability and change within vertebrate genomes," according to the abstract. As part of normal development, a lamprey "undergoes dramatic changes in the architecture of its genome."

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