Tumor’s unique "fingerprint" will help future cancer patients receive personalized, targeted treatments
BOSTON - February 25, 2008 - Researchers from Brigham and Women’s Hospital (BWH), for the first time, using new DNA sequencing technology, can identify the unique genetic mutations of a cancerous tumor of an individual patient. This new, more rapid and efficient approach may dramatically improve therapeutic decisions for cancer patients.
The researchers obtained the genetic sequences of all of the expressed genes in tumors from four patients with mesothelioma, an asbestos caused cancer of the lung. Three to four novel genetic mutations were found in each tumor, none of which had been implicated in cancer in previous studies. 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 accuracy of advanced new sequencing technology to identify the patient-specific genetic mutations in surgically removed tumor tissue and suggest that this approach could become a new standard for discovery of tumor mutations that underlie cancer. This approach points the way to individualized analysis of patient tumors thereby encouraging discoveries that have tremendous potential to highly refine individual patient care and guide therapy.
The BWH group developed new methods to preserve and select the optimal tissue from newly harvested tumors, and software tools to manage the billions of DNA sequence data points and discovered the important cancer causing genetic changes. This newly developed pipeline could be used to identify the genetic mutations in a given patient within a relatively short time frame, from a several weeks to just a few months.
BWH surgeons analyzed tissue from four malignant pleural mesothelioma tumors, one lung cancer specimen and from normal lung tissue. Approximately 266 megabases of cDNA were sequenced per patient using technology in collaboration with 454 Life Science Inc. All expressed genes were sequenced without any preconceived notion as to which may be more or less important. Analysis of the billions of DNA sequence data points was enabled by software developed in collaboration with the National Center for Genome Resources in Santa Fe, NM. The computer programs were designed to assemble the data and compare it among the patients and with public DNA and RNA databases to determine 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.
"We found that each tumor had its own unique genetic mutation, sort of like its own fingerprint," said David Sugarbaker, chief, Division of Thoracic Surgery at BWH, lead author of the study and a pioneer in mesothelioma research. "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. 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."
He added, "Technical advances are rapidly changing the way we can do mesothelioma research and advance personalized medicine at the clinical level. This step forward is akin to mainframe computers giving way to the desk top PC revolution. Ultimately, every patient’s tumor will be directly sequenced to determine its mutations and optimal treatment just as we now identify the cause of an infection before selecting the best antibiotic to treat it."
The research was supported by the International Mesothelioma Program at BWH. All the data will be made publicly available at the time of publication and can be accessed here.
For more information, contact BWH Media Relations at (617) 534-1600.
Brigham and Women’s Hospital (BWH) is a 747-bed nonprofit teaching affiliate of Harvard Medical School and a founding member of Partners HealthCare System, an integrated health care delivery network. BWH is committed to excellence in patient care with expertise in virtually every specialty of medicine and surgery. The BWH medical preeminence dates back to 1832, and today that rich history in clinical care is coupled with its national leadership in quality improvement and patient safety initiatives and its dedication to educating and training the next generation of health care professionals. Through investigation and discovery conducted at its Biomedical Research Institute (BRI), BWH is an international leader in basic, clinical and translational research on human diseases, involving more than 800 physician-investigators and renowned biomedical scientists and faculty supported by more than $400M in funding. BWH is also home to major landmark epidemiologic population studies, including the Nurses' and Physicians' Health Studies and the Women's Health Initiative.