Recently we’ve been looking at the challenges of interpreting and reporting variants found in genetic tests by clinical labs. In this final post in our miniseries, QIAGEN Bioinformatics’ Clinical Science Director Junaid Shabbeer walks us through the intricacies of handling data from genetic tests related to cancer.
Having been involved in directing the clinical lab at Myriad Genetics, Junaid has a lot of experience with variants detected in the BRCA1 and BRCA2 genes. When it comes to hereditary cancer, he says, the number of never-before-seen variants was always remarkably high. “For the BRCA genes, even after so many years of testing, we were still finding new variants,” Junaid tells us. Another example is Lynch syndrome, which is associated with a hereditary form of colon cancer.
For germline variants associated with hereditary cancer, the variant interpretation process aims to determine whether a variant is causative for the disease. In simple terms, lab directors, medical directors, and variant analysts are trying to determine if an observed variant in a specific gene from a patient is causing the observed phenotype or disease. Analysts track the variants reported from each test because the more often any given variant is observed, the more information can be collected for that variant to help accurately classify it. Over time, particular variants may be seen often enough that analysts become comfortable classifying them as benign or likely pathogenic. But for variants that are not well characterized, analysts must conduct a time-intensive and laborious variant scoring process to apply existing evidence toward an evaluation of whether the new variants are implicated in disease.
One of the big challenges for labs launching new hereditary cancer tests is dealing with soaring interest from patients and physicians. “For labs that had never offered hereditary cancer testing before, such as for BRCA genes, many find that they are not prepared to deal with the volume of demand when they launch a new test,” Junaid says. High demand means scores of novel variants observed, so analysts must determine whether those variants — most of which they are not yet familiar with, having just launched the test — are causative.
Interpreting variants for somatic cancer is a different process, as analysts are looking at DNA variants in a tumor to determine whether these variants are actionable or targetable, either with approved therapies or through prognostic or diagnostic data. The variants may also indicate how certain therapies are likely to affect a patient’s outcome. “In somatic cancer, where you’re sequencing to look for the molecular profile of a tumor, you’re seeking variants that are already well known to have a role in driving cancer,” Junaid says. Because scoring new variants is less important in this workflow, interpretation can be faster — although the rapidly expanding use of NGS-based tests for tumor assessment means that many clinical lab teams still face substantial demand for variant analysis services for this application.
Here at QIAGEN, we’re hoping to help alleviate the interpretation process with our newest application, the Ingenuity Clinical Decision Support platform. Currently available to early access customers, the tool will be showcased at this week’s AMP meeting in Maryland, where attendees are welcome to stop by our booths (#707 and #1023) for a demo. We hope to see you there!