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454 Detects Tumor Mutations Missed by Sanger


At least two teams of scientists have been exploring the ability of 454 Life Sciences’ platform to detect mutations in tumors, testing the potential advantages of massively parallel sequencing over traditional DNA sequencing for this application.

In the short term, these studies might help decide whether the Genome Sequencer 20 platform will become part of the NIH’s Cancer Genome Atlas pilot project.

The research could also bode well for other manufacturers of massively parallel sequencing technologies, among them Solexa, Helicos, and Agencourt. To be sure, these studies are early stage and involve just a small number of samples. But if the technologies hold up to their promise in these and other studies, they could pave the way for next-generation DNA sequencing technology to enter the potentially lucrative cancer diagnostic market.

“The promise of the new sequencing technologies is that they may allow accurate mutation detection for cancer genomes to be more rapid and economical,” says Greg Riggins, a Johns Hopkins University associate professor who is involved in one of the studies, sponsored by the National Human Genome Research Institute.

In fact, the “major finding” of the second study, performed by the Dana-Farber Cancer Institute, the Broad Institute, and 454 Life Sciences, was the tool’s ability to detect mutations “in samples where mutations had been invisible to Sanger sequencing,” according to Roman Thomas, a lead author of the study, which appeared online in Nature Medicine this June. What made 454’s technology stand out in this study was its ability to find mutations that were only present in a fraction of a clinical sample.

Meanwhile, researchers led by Bob Strausberg at the J. Craig Venter Institute have been sequencing glioblastomas, an aggressive form of brain cancer, in an NHGRI-sponsored pilot study that compares traditional Sanger sequencing and 454’s pyrosequencing approach.

— Julia Karow


US Patent 7,065,451. Computer-based method for creating collections of sequences from a dataset of sequence identifiers corresponding to natural complex biopolymer sequences and linked to corresponding annotations. Inventors: Harold Garner and Amit Kulkarni. Assignee: Board of Regents, The University of Texas System. Issued: June 20, 2006.

“The invention relates to computer-based systems and methods for the design, comparison and analysis of genetic and proteomic databases,” according to the patent abstract. The technique uses a computer tool that “takes in a large collection of sequence identifiers and associates it with other information collected from many sources like sequence annotations, pathways, homology, polymorphisms, artifacts, etc.”

US Patent 7,085,651. Method and device for assembling nucleic acid base sequences. Inventors: Tomohiro Yasuda and Tetsuo Nishikawa. Assignee: Hitachi. Issued: August 1, 2006.

This patent relates to “the clustering and assembling of nucleic acid base sequences at a high speed,” according to its abstract. “The clustering and assembling are performed by repeatedly [performing the patented procedure] based on greedy method until no unprocessed input nucleic acid base sequence is left.”


454 Life Sciences and the Max Planck Institute for Evolutionary Anthropology announced plans to sequence the complete Neanderthal genome. During the two-year project, which will be supported by a grant from the Max Planck Society, the sequencing team will reconstruct a draft of the 3 billion-base genome using samples gathered from several Neanderthal individuals.

Solexa met its promise to begin shipping an early version of its first sequencing instrument to early-access customers by the end of June. Among the first recipients of the company’s Genome Analysis System were the Broad Institute and the Genome Sequencing Center at the Washington University School of Medicine. Solexa plans to launch the instrument broadly later this year. In other news, Solexa hired Brock Siegel, who spent the last 15 years at Applied Biosystems, as its chief operating officer.

The Joint Genome Institute has sequenced and analyzed the genome of Laccaria bicolor, a fungus that forms a beneficial symbiosis with trees. The sequence may shed light on biomass production and carbon management.

In reporting its fiscal fourth-quarter earnings, Applied Biosystems said that revenue increased nine percent, buoyed by real-time PCR and mass spec sales. DNA sequencing sales, however, slid around four percent for the quarter to $137.8 million.



NHGRI’s latest sequencing targets include a project to sequence as many as 50 strains of the yeast Saccharomyces cerevisiae. Other targets include the Northern white-cheeked gibbon, a set of fungi known as dermatophytes, and seven mammals that will be upped from draft coverage to high-density sequence.

The Scan

Coral Genome Leads to Alternative Amino Acid Pathway Found in Other Non-Model Animals

An alternative cysteine biosynthesis pathway unearthed in the Acropora loripes genome subsequently turned up in sequences from non-mammalian, -nematode, or -arthropod animals, researchers report in Science Advances.

Mosquitos Genetically Modified to Prevent Malaria Spread

A gene drive approach could be used to render mosquitos unable to spread malaria, researchers report in Science Advances.

Gut Microbiomes Allow Bears to Grow to Similar Sizes Despite Differing Diets

Researchers in Scientific Reports find that the makeup of brown bears' gut microbiomes allows them to reach similar sizes even when feasting on different foods.

Finding Safe Harbor in the Human Genome

In Genome Biology, researchers present a new approach to identify genomic safe harbors where transgenes can be expressed without affecting host cell function.