Year in review: Cancer genetics grows up

Not all mutations are alike, or problematic

melanoma cells

INDIVIDUALITY  Genetic analyses of tumors (melanoma cells shown) offer great promise for improving diagnoses and treatment, but new studies show that not all mutations can be treated equally.

Julio C. Valencia/NCI Center for Cancer Research

Personalized genomics has been heralded as the next big weapon in the war on cancer. But researchers analyzing various tissue types this year, looking for mutations linked to the disease, have found that not all genetic alterations should be targeted equally.

“Genetics is changing oncology for the good,” says Benjamin Kipp, an expert in clinical genetics at the Mayo Clinic in Rochester, Minn. “But overinterpretation can harm the patient.”

Genetic profiles of tumors offer unprecedented opportunities for both cancer diagnostics and for doctors planning treatment. Bowel cancer tumors with mutations in the KRAS gene, for example, respond poorly to the drug cetuximab; the skin cancer drug vemurafenib works only if melanomas have a particular mutation in the BRAF gene.

But such genetic testing can be misleading if it isn’t conducted alongside tests of healthy cells from the same person, says oncologist Victor Velculescu of the Johns Hopkins University School of Medicine. He led a vast analysis comparing the genetic profiles of tumors and normal tissue of more than 800 cancer patients and found that nearly two-thirds of mutations in the studied tumors — many of which might be used to guide treatment — also showed up in patients’ healthy tissues (SN: 5/16/15, p. 10). For those patients, the mutations were probably just benign variants unrelated to the cancer. Analyzing healthy tissue can also reveal whether mutations found in tumors are heritable or not, Velculescu says, which is important for deciding whether a cancer patient’s family should receive genetic counseling.

Cancer-linked mutations are surprisingly common in healthy eyelid skin. Colors show mutated genes; circles indicate the size of the skin patch carrying the mutation. I. Martincorena, I. Martincorena et al/Science 2015
Complicating matters further is the fact that even mutations that have been linked to cancer will not always manifest as cancer. A study published in May examining eyelid skin discovered numerous cancer-associated mutations in normal, healthy patches of the skin ( SN: 6/27/15, p. 8 ). Detecting these mutations might lead to great anxiety and unnecessary, sometimes invasive treatments.

As genetic testing of tumors becomes more widespread, best practices will emerge, as will a better understanding of the disease. “We are trying to change the way we look at cancer,” says Sameek Roychowdhury, a medical oncologist at the Ohio State University Comprehensive Cancer Center in Columbus. “But we are just seeing the tip of the iceberg.”

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