NCGR Software Enables Identification Of Mutated Genes Unique To Mesothelioma Tumors

Main Category: Asbestos / Mesothelioma
Also Included In: Genetics;  IT / Internet / E-mail
Article Date: 27 Feb 2008 - 1:00 PDT

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The National Center for Genome Resources (NCGR) announced the launch of the first web-based software system specifically designed for analysis of ultra-high throughput DNA sequencing projects. The new software system, AlpheusTM, will enable researchers to achieve highly scientifically meaningful results from massive DNA sequencing projects. Researchers from Brigham and Women's Hospital (BWH) announced today that they had employed AlpheusTM to discover the unique genetic mutations of cancerous tumors in individual patients. This new approach may dramatically improve therapeutic decisions for cancer patients.

BWH researchers used AlpheusTM to analyze the DNA sequences of all genes expressed in tumors from four patients with mesothelioma, an asbestos caused cancer of the lung. Approximately 266 million bases of expressed genes were sequenced per patient in collaboration with 454 Life Sciences, Inc., and analyzed with AlpheusTM software. AlpheusTM was collaboratively developed with BWH researchers to pipeline ultra-high throughput DNA sequences, enabling comparisons between patients and with reference databases to identify candidate mutations, which were validated by independent methods. In the four mesothelioma tumors 15 novel mutations of multiple types were discovered and each mesothelioma tumor had a unique mutation profile. None of the mutated genes has ever been implicated in mesothelioma. Each tumor had a unique mutation profile, similar to having a unique fingerprint. The research results are published in the February 25, 2008 issue of the Proceedings of the National Academy of Sciences.

The findings confirmed the usefulness of the AlpheusTM system to identify patient-specific mutations in massive numbers of DNA sequences from tumor tissues and suggest that this approach could become a new standard for discovery of mutations that underlie cancer. This approach points the way to individualized analysis of patient tumors thereby encouraging discoveries that have tremendous potential to refine individual patient care and guide therapy.

"One truly encouraging aspect of our findings is after spending a year and a half to develop the methodology and software for the pipeline, new tumors can be analyzed over the course of about a month," said David Sugarbaker, chief, Division of Thoracic Surgery at BWH, lead author of the study. "Knowing which genes are mutated opens the door to better understanding and the discovery of more targeted and effective patient-specific treatments in real time."

The research was supported by the International Mesothelioma Program at BWH (http://www.impmeso.org). All the data will be made publicly available at the time of publication.

BWH is a 747-bed nonprofit teaching affiliate of Harvard Medical School and a founding member of Partners HealthCare, an integrated health care delivery network. For more information about BWH, please visit www.brighamandwomens.org.

NCGR is a nonprofit 501(c) 3 organization whose mission is to improve health, nutrition and the environment by genome sequencing and analysis. To learn more about NCGR, visit http://www.ncgr.org.