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Exploring biological functions that trigger tumor formation

PROFILE: RICCARDO DALLA-FAVERA | PATHOLOGY & CELL BIOLOGY

Thirty years ago, recombinant DNA technologies were in their infancy, and Riccardo Dalla-Favera was a 20-something researcher searching for elusive evidence that cancer is caused by molecular changes in DNA. 

Then one morning in 1982, while working as a visiting fellow at the National Cancer Institute, he and his team made a discovery that would profoundly impact the field of cancer research. They identified the first human “oncogene” – a gene that helps transform a normal cell into a tumor cell. For him, that golden moment when he found the mutated DNA of an oncogene “is what research is all about.”

“It was thrilling to think that this work would end up in textbooks and people would study it for years to come,” says Dalla-Favera, who earned his MD from the University of Milan and specializes in hematology and the molecular genetics of cancer and lymphoma. “Fortunately, research is full of such exciting moments.”

Dalla-Favera’s discovery involved “c-Myc”, a cancer gene normally located near the end of human chromosome number 8. Dalla-Favera found that the gene had somehow jumped to chromosome 14 in people suffering from a specific form of lymphoma – and in doing so, it apparently converted a normal cell into a cancerous cell.

At the time, one of the world’s leading cancer researchers called it the “most compelling evidence” yet that oncogenes are responsible for human cancer – a theory accepted today as common wisdom in medicine. Indeed, oncogenes now provide the most promising targets for the latest generation of cancer drugs.

Dalla-Favera, the founding Director of the Institute for Cancer Genetics at Columbia University, continues to make groundbreaking discoveries and remains a prominent leader in the field of molecular oncology. With the benefit of new technologies, his research group can now scan the entire genome of a lymphoma to catalog the full spectrum of cancer-causing genetic abnormalities, information that should yield improved, and ultimately more personalized, therapy for cancer patients. 

Dalla-Favera is also elucidating the underlying mechanisms by which altered oncogenes promote cancer development, in part by designing mouse models of the lymphomas that afflict people.  In addition, he’s researching “BCL-6”, another important oncogene from lymphoma patients that he discovered in 1991. Interesting, BCL-6 codes for transcription factor that controls the behavior of other genes in B cells. Thus, to counter its cancerous activity in lymphoma patients, Dalla-Favera is examining how BCL-6 functions in both normal and pathological cells and developing novel ways to inactivate it in tumor cells. 

As it approaches the 30th anniversary of his original discovery, Dalla-Favera continues to study the c-Myc oncogene, exploring its biological functions and how it can move from one chromosome to another in a manner that triggers tumor formation.  While the thrill of pure scientific investigation still endures, as new cancer drugs directed at oncogenes are successfully introduced into the clinic, Dalla-Favera can now experience another benefit of research.   “There’s a real satisfaction in seeing the positive impact of our laboratory work on the lives of lymphoma patients”. 

To view technologies from Dr. Dalla-Favera's lab, please click here