Understanding the Genetic Makeup of Your Tumor

"It’s the standard of care for every woman with ovarian cancer to get what’s called germline testing," says Dr. John Nakayama, gynecologic oncologist at University Hospitals Cleveland Medical Center. "That’s looking at your actual genes."

Germline testing detects certain mutations throughout your body that put you at risk for ovarian cancer. Because these mutations pass from parent to child, the results can inform you about whether other family members might be at risk.

The most common type of germline mutation found in women with ovarian cancer is a BRCA gene mutation, which is commonly passed down among family members. While the average lifetime risk of getting diagnosed with ovarian is about  1.3%, the chance of a woman with a BRCA gene mutation getting ovarian cancer can be as high as 44%.

Testing your genes is just one piece of the puzzle. According to Dr. Nakayama, tumors can harbor gene mutations that might not be within your germline.

Testing the Tumor 

A tumor can be tested in a number of different ways. One method is to send it to a lab for a process called next-generation sequencing, which examines the tumor, looking at a battery of about 70 to 80 different genes. This sequencing can detect BRCA, as well as other genetic mutations, such as the genes that cause the inherited condition Lynch syndrome and other types of cancer.

"The other option, which isn’t looking at the actual genes of your tumor, is to do something called a homologous recombination deficiency score," says Dr. Nakayama. "Homologous recombination deficiency is when your DNA doesn’t repair well. It's actually the way that BRCA mutations work."

Other gene mutations can also impact these DNA repair defects. Testing the tumor for these mutations is critical when determining the next phase of treatment.

"It makes sense, because if you can’t repair your DNA well, then you’re more likely to get cancer because the gene mutations that are in you are building up," adds Dr. Nakayama. "And you’re just more likely to have one of those mutations that lets [the cell] turn into cancer. And we can take advantage of that."

For example, your homologous recombination deficiency status may help predict how you'll respond to certain types of chemotherapy. Also, experts now know that women with the BRCA mutation benefit the most from PARP inhibitors, a type of drug therapy that specifically targets those damaged cells.

"That’s probably the coolest thing about this. Yeah, you are more likely to get cancer, but at the same time, now we have classes of drugs that are developed specifically for people like that. And the change in their outcomes is somewhat remarkable,” Dr. Nakayama says.

The Future of Tumor Testing

Researchers are continuing to learn more about the genetic makeup of tumors and how best to treat them. One question experts are asking is: Are all the tumors within an individual patient the same?

"That’s something we’re wrestling with right now," says Dr. Nakayama. "Do you biopsy one tumor and make the assumption that they’re all the same? Or do you biopsy multiple tumors, even if that comes with its own problems and costs?"

What investigators eventually learn will likely help to reshape the future of tumor testing, as well as treatment. But for now, women can at least learn the genetic makeup of their tumor, so their doctors can more appropriately target their treatment.

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