Frontline Cancer: Genetic background can provide clues about possible future tumors

FRONTLINE CANCER:

In Steven Spielberg's 2002 science fiction thriller "Minority Report," Tom Cruise leads a futuristic police unit whose job is to prevent crimes based upon three mutated humans called "precogs" who "previsualize" crimes via visions of the future. In other words, the precogs predict where and when something bad is going to happen. It's Cruise's job to make sure it doesn't. The notion is fantastic, originally conceived by novelist Philip K. Dick, with an emphasis on the definition of fantastic — to be imaginative, fanciful, remote from reality.

Or not. "Minority Report" was Hollywood fantasy, but a research article published in the journal Cancer Discovery earlier this year suggests the idea isn't so far-fetched, at least in terms of potentially predicting and preventing individual cancers. Hannah Carter, Ph.D., assistant professor of medicine, and Trey Ideker, Ph.D., professor of medicine and genetics, both at UC San Diego School of Medicine and Moores Cancer Center, are the first and senior authors of the article, respectively.

"Our findings suggest that a person's genetic background can provide clues about what their tumor might look like if they did happen to get cancer, including where it might occur and what mutations might appear," said Carter, a recipient of the prestigious NIH Early Independence Award, which is designed to accelerate the research of exceptional scientists early in their careers. It's well known that a person's genetic background plays an important role in cancer. We are all vulnerable or predisposed, in varying degrees, to different kinds of cancer based upon our genes or mutations.

"Researchers tend to focus on genetic cancer risk or on DNA mutations in tumor genomes," said Carter, "but they don't often relate the two. We did a genome-wide screen looking for inherited genetic variation that directly affects observable characteristics of tumors." Specifically, Carter and colleagues tested more than 2 million genetic variants in 10,000 cancer patients participating in The Cancer Genome Atlas, an ongoing, national effort to catalog genetic mutations responsible for cancer.

"We found more than 400 variants that influence either the tissue site where a tumor emerges or the genes that are mutated in that tumor's genome," Carter said. "Some of the variants affected nearby genes that were performing similar functions to the mutated genes in the tumor, providing new clues to unravel how an individual's genetic background shapes the genetic landscape of their tumor." In essence, the researchers revealed a landscape of common germline variants (mutations in heritable genetic material) that influence how and where tumors develop. It's a possible preview of what kind of cancer might appear later in a patient's life — and where.

"This type of information could help improve screening to detect tumors and maybe even allow pre-emptive design of drug combinations that will be effective," said Carter. "Now we need follow-on studies with much larger numbers of patients to really map out this landscape and determine how to best use it to fight cancer."

In past columns, I've written that the best cancer treatment is the one that prevents cancer altogether. Modern medicine and common sense (exercise, eat right, don't smoke) are already driving that effort with measurable success. Carter, Ideker and colleagues are writing the next chapter — and maybe the future-forward script for another Hollywood movie.

 

Scott M. Lippman, M.D., is director of UCSD Moores Cancer Center. His column appears in La Jolla Light the fourth Thursday of each month. You can reach Dr. Lippman at mcc-dir-lippman@ucsd.edu

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