Large Scale Program Launched to Scan Tumors for Mutations and Establish Genomic Database

Focused on speeding the development of cancer treatments that target the genetic flaws in each patient’s tumor, two internationally known medical institutions based in Boston, MA, USA, have launched Profile, a major research effort to scan tumor tissue from adult cancer patients for hundreds of gene mutations linked to cancer.

The program, undertaken by investigators from Dana-Farber Cancer Institute and Brigham and Women’s Hospital, almost two years in development, is one of the most extensive research projects in cancer genomics yet undertaken nationally. Open to every adult cancer patient seen in the Brigham and Women’s and Dana-Farber Longwood Medical Area clinics, the program aims to build a comprehensive database for research into the genetic composition of different cancer types, and ultimately, into treatments that are most effective against individual tumors. (The program will be extended to pediatric cancer patients at Dana-Farber and Children’s Hospital Boston in 2012.)

Clinicians at Dana-Farber/Brigham and Women’s Cancer Center currently use targeted therapies that pinpoint genetic mutations in a select number of cancers, including colon, lung, breast, and some leukemias and sarcomas. The new research program is focused on identifying a far greater number of mutations for a wider array of cancers, ultimately enabling clinicians to treat more cancers with targeted therapies in the future.

“Profile will put us firmly on the path to realizing the promise of personalized medicine. By ‘genotyping’ each tumor--identifying the set of mutations that drive it--we’ll be able to design therapies geared specifically to those mutations, depriving the tumor of the ability to sustain itself while producing a minimum of side effects,” says Dana-Farber’s Chief Scientific Officer Barrett Rollins, MD, PhD, one of the architects of the program. “We’re laying the foundation for the development, testing, and implementation of such therapies, and we expect the project to grow as we discover new cancer-related gene mutations and with the development of new technologies.”

Tissue testing for the program will be performed with OncoMap, a system custom designed for genomic research in cancer by investigators at Dana-Farber, the Broad Institute of the Massachusetts Institute of Technology (MIT) and Harvard University (Boston, MA, USA; Cambridge, MA, USA). Using high-speed, high-capacity robotic machinery to prepare, sort, and scan tumor tissue, the system makes it possible to process rapidly large numbers of tumor tissue samples with a high degree of accuracy.

“We’ve learned a great deal about the role of specific mutated genes in cancer, and we now have technology for testing large numbers of tumor samples for those mutations,” said Janina Longtine, MD, director of molecular diagnostics at Brigham and Women’s Hospital and a senior leader of the research program. “For the first time, we have the opportunity to build a critical mass of genomic data that can be used to bring better treatments to patients.”

Studies have shown that tumors that look and act alike can carry different sets of mutations, which influence how cancers grow, metastasize, and respond to treatment. Only by gathering data on a mass scale can researchers expect to capture the huge diversity of cancer at the genetic level, according to the program leaders. By identifying a tumor’s molecular characteristics, clinicians will be able to select the appropriate treatment for the each patient. A patient whose tumor carries a specific mutation would receive a drug known to be effective against that mutation in specific types of tissue. Although this currently occurs in a minority of cancer cases, the aim of the Dana-Farber/Brigham and Women’s project is to find ways to apply this to many more patients.

In contrast to programs that scan specific types of tumors for a small number of gene mutations, Profile tests tumor samples for nearly 500 cancer mutations in 41 genes. Program researchers anticipate that well over 10,000 people will participate in the program during the first year and every year thereafter.

Study participants will have their tumor tissue scanned and data from their medical record--on the course of their disease, its response to treatment, relapse, and side effects--will be placed in a second, separate database. By connecting data from these two sources, researchers will be able to study which therapies are most effective against particular tumor types.

The study participants also can have the results of their OncoMap testing sent to their Dana-Farber or Brigham physician. The tumor-testing program was developed mainly for research purposes, but leaders expect that some participants may immediately benefit by learning of their eligibility for current clinical trials.

Drs. Longtine and Rollins anticipate that Profile will expand with the discovery of additional cancer-related mutations and the development of more sophisticated screening technologies.

Related Links:
Dana-Farber Cancer Institute
Brigham and Women’s Hospital
Broad Institute