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Breakthrough in DNA Sequencing


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Dana Farber and 454 Life Sciences Announce Breakthrough in DNA Sequencing for Cancer Research

- Sequencing Method Detects Cancer Mutations at the Molecular Level -

BRANFORD, Conn., June 25 /PRNewswire/ -- 454 Life Sciences Corporation,

a majority-owned subsidiary of CuraGen Corporation (Nasdaq: CRGN), in

collaboration with scientists at Dana Farber Cancer Center and Broad

Institute, today reported a new method for the detection of cancer gene

mutations present at extremely low levels. The research, published online

(ahead of print) in the journal Nature Medicine, describes how the 454

Sequencing method identifies rare cancer-associated genetic variations

at the molecular level, potentially enabling the personalization of

targeted therapies. The title of the article is: 'Sensitive mutation

detection in heterogeneous cancer specimens by massively parallel picoliter

reactor sequencing.'

454 Sequencing technology was used to analyze mutations in five

exons of the Epidermal Growth Factor Receptor (EGFR) gene in tumor samples

from 22 patients with lung cancer. The EGFR gene is the target for several

new anti- cancer drugs called EGFR inhibitors. This research proposes that

454 Sequencing may help to validate the ability of EGFR mutations to

predict patient responsiveness to treatment with an EGFR inhibitor.

It has been realized that genetic mutations are responsible for

sensitizing some tumor cells to chemotherapy, while other mutations render

tumor cells completely resistant to drug treatments. Historically, research

progress has been slowed by the complex mix of cells in a tumor sample,

compounded by cost-prohibitive, conventional low-resolution sequencing

methods that lack sufficient accuracy to characterize the DNA in cancerous

cells. 454 Sequencing is the first advanced sequencing technology that

can generate hundreds of thousands of DNA sequences in one run, rapidly and

comprehensively conducting high-throughput nucleotide sequencing, with

specific application to sequencing of whole genomes and ultra-deep

sequencing of target genes. By enabling a method of sequencing that is more

comprehensive and less expensive than conventional sequencing methods, 454

Sequencing may be used in medical research settings to detect

cancer-associated genetic mutations.

"Analysis of DNA from tumors is complicated by varying amounts of tumor

cells in patient samples. Furthermore, the heterogeneous nature of many

tumors makes it difficult to accurately sequence the tumor DNA, which is

required in order to personalize treatment," explained senior author of the

study, Matthew Meyerson, M.D. Ph.D., of Dana Farber Cancer Center and Broad

Institute. "454 Sequencing may facilitate accurate molecular diagnosis of

heterogeneous cancer specimens and enable patient selection for targeted

cancer therapies," added Meyerson.

The technology is already being explored at other institutions. "We

have validated 454 Sequencing for medical sequencing on a gene target of

interest," stated Robert Strausberg, Ph.D. Deputy Director and Vice

President of Human Genomic Medicine at The J. Craig Venter Institute. "The

method is not only very sensitive, but it is also quantitative and provides

a digital display of gene variation within tumors. We have already

identified a mutation missed by our previous sequencing approach," said

Strausberg.

"The publication of this paper demonstrates the versatility of our

system and its ability to enable medical research that has been considered

impractical until now," stated co-author Michael Egholm, Ph.D., Vice

President of Molecular Biology at 454 Life Sciences. "454 Sequencing can

open new research opportunities through its low cost, high throughput, and

superior sensitivity. The ability to sequence entire exons in a single read

is unique to 454 Sequencing among the commercially available, next

generation sequencing technologies. Ultimately, we hope our system will

enable personalized medicine, such as identifying the early stages of drug

resistance and facilitating a change in treatment that is tailored to a

patient's unique genetic response," added Egholm.

About 454 Life Sciences

454 Life Sciences, a 66% majority-owned subsidiary of CuraGen

Corporation (Nasdaq: CRGN), is commercializing novel instrumentation and

measurement services for rapidly and comprehensively conducting

high-throughput nucleotide sequencing, with specific application to

sequencing of whole genomes and ultra-deep sequencing of target genes. 454

Life Sciences' Genome Sequencer 20 System enables one individual to prepare

and sequence an entire genome after performing a single sample preparation,

irrespective of the size of the genome being studied. The hallmark of 454

Life Sciences' technology is the PicoTiterPlate, which allows a single

instrument using patented light emitting sequencing chemistries to produce

over 20 million nucleotide bases per five- hour run, totaling more than 60

times the capacity of instruments using the current macro-scale technology.

For additional information on 454 Life Sciences, please visit

http://www.454.com . For additional information on the Genome Sequencer 20

System and reagents, please visit http://www.roche-applied-science.com .

Safe Harbor

This press release contains forward-looking statements that are subject

to certain risks and uncertainties. These statements include statements

that 454 Sequencing (i) may validate the power of EGFR mutations to

predict patient responsiveness to treatment with an EGFR inhibitor, (ii)

may be used in medical research settings to detect cancer-associated

genetic mutations, (iii) may facilitate accurate molecular diagnosis of

heterogeneous cancer specimens and enable patient selection for targeted

cancer therapies, (iv) may enable medical research that has been considered

impractical until now through its low cost, high throughput, and superior

sensitivity, and (v) may enable personalized medicine, such as identifying

the early stages of drug resistance and facilitating a change in treatment

that is tailored to a patient's unique genetic response. Such statements

are based on management's current expectations and are subject to a number

of risks and uncertainties that could cause actual results to differ

materially from those described in the forward- looking statements. 454

Life Sciences and CuraGen caution investors that there can be no assurance

that actual results or business conditions will not differ materially from

those projected or suggested in such forward-looking statements as a result

of various factors, including, but not limited to, the following: the early

stage of development of 454 Life Sciences' products and technologies;

customer acceptance of 454 Life Sciences' products and technologies; 454

Life Sciences' ability to scale-up production of its products and

technologies; disputes between 454 Life Sciences and CuraGen; the success

of competing products and technologies; technological uncertainty and

product development risks; uncertainties of clinical trials, government

regulation and healthcare reform; uncertainty of additional funding with

respect to both CuraGen and 454 Life Sciences; 454 Life Sciences' and

CuraGen's history of incurring losses and the uncertainty of achieving

profitability; CuraGen's stage of development as a biopharmaceutical

company; patent infringement claims against 454 Life Sciences' and

CuraGen's products, processes and technologies; the ability to protect 454

Life Sciences' and CuraGen's patents and proprietary rights; uncertainties

relating to commercialization rights; product liability exposure; and

competition. Please refer to CuraGen's Annual and Quarterly Reports on

Forms 10-K and 10-Q for a complete description of these risks. 454 Life

Sciences and CuraGen disclaim any intention or obligation to update or

revise any forward-looking statements, whether as a result of new

information, future events, or otherwise, unless required by law.

454® is a registered trademark of 454 Life Sciences Corporation. 454

Life Sciences, Genome Sequencer 20, PicoTiterPlate, and 454

Sequencing are trademarks of 454 Life Sciences Corporation.

Contact:

454 Life Sciences Noonan Russo

Peter Dacey Benjamin Carmichael

Vice President, Finance benjamin.carmichael@eurorscg.com

info@454.com +1-212-845-4242

(877) 890-GNOM

SOURCE 454 Life Sciences

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Related links:

http://www.454.com

http://www.roche-applied-science.com

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A United Business Media company.

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