Dr. Alice Berger is devoting her career to unraveling the tangled web of cancer genetics, but it’s an avocation that she arrived at after already completing her undergraduate degree — in chemistry.
“I didn’t take a single biology class in college,” the lung cancer researcher and recent Human Biology Division recruit recalled. Her first post-graduation job was in an immunology research lab at the University of Virginia, where Berger was also able to take graduate-level biology courses.
“As soon as I started learning about proteins, I thought they were the most amazing chemistry you could imagine,” she said.
One class in particular focused on the genetics of cancer cells. For Berger, it was fascination at first encounter.
“I thought that cancer was really interesting because by learning how normal cell biology gets messed up, you can also learn something about how [cells function] normally,” said Berger. “I thought that was a really interesting way to learn about genetics and cell biology.”
The human genome sequence was published not long after, and increasing information about tumors’ DNA sequences also increasingly complicated scientists’ picture of cancer, she said.
Our cells use the DNA sequence of genes as recipes for building proteins. Mutations are “typos” that change genes’ sequences and can affect whether proteins are built or how they function once created. Certain mutations are highly associated with cancer, but it’s not always clear from reading the typos in a particular gene’s DNA sequence what specific consequences these changes will have. These mutations are known as “variants of unknown significance,” and they are part of why the picture of cancer is so complex.
Berger has made it her mission to uncomplicate this picture — as quickly as possible. New technologies enable researchers to identify new mutations at an ever-accelerating pace, but because of the time it takes to clarify the significance of these variants, mutations that could have tantalizing implications for patient care pile up as the painstaking work to assess their impact lags.
Berger has developed a technique to evaluate, in one go, how hundreds of variants of unknown significance influence the function of the proteins encoded by their genes. This is the first step toward determining whether a particular genetic typo promotes cancer development and, therefore, might have the potential to form the basis of a new targeted treatment. Berger’s technique dramatically enhances the speed at which researchers can begin to understand how different gene variants contribute to disease.
“As soon as I started learning about proteins, I thought they were the most amazing chemistry you could imagine.”
In addition to helping researchers take a bird’s eye view of cancer genetics, Berger is peering in detail at the role of particular genes in lung adenocarcinoma. She discovered that a gene known as RIT1 is often mutated in lung adenocarcinoma, and she demonstrated that mutations in RIT1 drive cancer formation. She is currently working to better understand the function of RIT1 and identify the molecular pathways it regulates, in order to discover new therapeutic targets.
Berger’s ultimate goal is not research fame but improved patient care. She already knows the satisfaction of producing findings that help patients. Berger collaborated on the analysis of mutations in lung adenocarcinoma, which revealed that 5 percent of patients had a rare type of mutation in a gene known as MET. The study prompted doctors to give drugs that inhibit MET to lung cancer patients who exhibit these mutations, some of whom are responding positively to the new treatment.
“It’s really rewarding to think I may have played a small role in those inhibitors being paired with that [mutation],” said Berger.
Now the head of her own lab at Fred Hutch, Berger is taking advantage of close connections with oncologists to learn about what new research directions may have the most promise for patients.
— By Sabrina Richards, Feb. 10, 2017