Guiding Genomics Use in Cancer Care

Five major cancer organizations are combining forces to propose standards for applying next-generation sequencing to clinical practice.

The Actionable Genome Consortium (AGC) was founded by Dana-Farber Cancer Institute (Boston, MA), Fred Hutchinson Cancer Research Center (Seattle, WA), The University of Texas MD Anderson Cancer Center (Houston), Memorial Sloan Kettering Cancer Center (New York, NY), and the genome-sequencing company Illumina (San Diego, CA). The group plans to define what constitutes an “actionable event” in individual tumors and to recommend best practices for biopsy, sample storage and transport, and DNA extraction; technical performance standards for DNA sequencing; standards for variant identification, annotation, and interpretation used in whole-genome sequencing; and guidelines for the format and content of clinical reports.

“We want to come up with a panel of therapeutic targets that make sense in terms of medical implications and cost,” says Barrett Rollins, MD, PhD, chief scientific officer at Dana-Farber. “We're focusing on the baseline things that an oncologist would want to know about every patient's tumor to order tests that have direct clinical applicability or are very likely to.”

For example, the standards might be used to justify testing for specific genetic alterations in non–small cell lung cancers, such as EGFR mutations or ALK rearrangements, that could be targeted with FDA-approved drugs, he says. Insurance companies would use the standards to determine coverage for tests that may improve clinical outcomes.

Knowing the genetic composition of a tumor may also help oncologists match patients to appropriate clinical trials, says Illumina's Robert Cohen, MBA, director of the AGC.

“In the future, the signature of a tumor will be measured or attempted to be measured in every cancer patient, and that signature should be one way that patients are matched to clinical trials,” he says. “Enrollment of all appropriate patients in clinical trials would become the standard of care.”

A research arm of the consortium will pursue collaborative projects tackling major issues in molecular oncology, says Cohen. One area of focus will be the potential clinical utility of circulating nucleic acids—for example, whether they could be used as a surrogate for tumor biopsies when tissue-based diagnosis is not possible, such as in patients with bone-only metastases.

The AGC plans to publish its recommendations in early 2015, says Cohen. The group will then work with national cancer organizations to develop official guidelines based on the recommendations.

“The time is right to create uniform standards for the molecular analysis of tumors,” says Eric Holland, MD, PhD, director of solid tumor translational research at Fred Hutchinson. “We're going from a phase of scientific discovery to implementation and what it really means to society.”

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