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Agencourt
Aids In Pivotal Cancer Find
Discovery
of 200 genes not previously linked to breast and colon cancers
By Nina Flanagan
November/December
2006
Scientists recently
discovered 200 mutated genes not previously linked to breast and colon
cancers. Researchers at Johns Hopkins Kimmel Cancer Center in Baltimore
published their findings online in the September 7, 2006 issue of Science
Express. The study provides insight into disease processes that may serve to
drive cancer research forward.
Working with Agencourt Bioscience
Corporation, Hopkins began with twenty-two tumor samples of breast and colon
cancers, and compared normal genetic codes with those of the tumor samples.
Within each sample, the Hopkins researchers
examined the DNA code of 13,000 genes identified by The Human Genome Project
Each gene was divided into ten overlapping
sections resulting in 130,000 sections for analysis. Each section was
amplified, purified, and its sequence determined using more than three
million biochemical reactions.
"What they did at Hopkins was almost
like a draft of the cancer genome. This is the first big study that's been
done like this, and the data from it identified genes previously known to be
involved with these cancers as well as many new genes [sic]," says Lynn
Doucette-Stamm, vice president of business development at Agencourt.
Doucette-Stamm said that it made sense for Agencourt to work on this project
because the company has been providing sequencing services to Johns Hopkins.
SoftGenetics LLC made the detection software, called Mutation Surveyor,
along with a special database for the study.
Agencourt's Genomic Services division offers
sequencing services to customers, ranging from high-throughput (up to 80,000
sequences per day) to single-tube sequencing. The company's SPRI technology
(Solid Phase Reversible Immobilization) is the key feature of the genomic
services workflow and automation. SPRI uses paramagnetic microparticles to
immobilize nucleic acids. Contaminants are then removed without filtration
or centrifugation. SPRI provides higher yields than column-based methods,
requires no organic solvents, and is scalable.
Researchers entered the resulting sequences
into computer software programs to match normal sequences with those from
tumor samples. More than 800,000 suspicious regions were highlighted and
visually inspected to verify mutations. The 200 significantly mutated genes
in the breast and colon cancer samples were distinct, suggesting that each
cancer developed its own unique pathway.
"These data lay the foundation for
decades of research on colon and breast cancers," says Victor
Velculescu, assistant professor of oncology at the Johns Hopkins Kimmel
Cancer Center.
This marks the third major cancer research
project for which Agencourt, a Beckman Coulter company, has provided
sequencing services. The other two projects involved mutations in lung
cancer and chronic myelomonocytic leukemia. Agencourt has relationships with
other cancer centers including the University of Texas MD Anderson center,
Harvard University's Dana Farber, and Memorial Sloan-Kettering.
"I know this study will open doors for
[more] larger studies because people have seen that is actually leads to
very fruitful data, so there's going to be a flurry of new projects in major
cancer centers to start looking at cancers on a more global spectrum,"
Doucette-Stamm commented. To become involved in similar projects,
"we're going to have to move into the next-generation sequencing
platforms," she says.
Scientists at Agencourt are currently
evaluating which new high-throughput platforms they will need to bring
online. According to Doucette-Stamm, Agencourt plans to continue building
its genomic services. Based on Agencourt's experience with the the Johns
Hopkins study, "we're very interested in expanding our cancer genomics
projects because we have a lot of experience and it's a hot area now,"
Doucette-Stamm stated.
Agencourt recently launched the FormaPure
System, which can analyze paraffin-embedded samples and process up to 96
samples in four hours. Paraffin-embedded cancer tissue samples contain
significant amounts of related clinical data, yet researchers have been
reluctant to use these samples because they lack robust methods for
isolating DNA and RNA from the samples. The FormaPure System also uses the
SPRI paramagnetic technology, which allows researchers to process a few to
hundreds of samples per day.
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