Genomics in Clinical Practice, Part 1: The Rise of Multiplex Gene Testing for Cancer

Kate M. O'Rourke


July 20, 2016

In This Article

Editor's Note:
This is the first in a three-part series on Medscape Oncology designed to update and familiarize practicing oncologists with the most important issues in multiplex and genomic testing.

In the 20 years since the first cancer gene test became available, the number and variety of tools available to clinicians for genetic analysis has exploded, far outpacing researchers' understanding of their clinical use. At the recent annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago, experts discussed the rise of multiplex gene panels and what new studies show about their integration in cancer care.

Single-Gene Assays Give Way to Multiplex Testing

The cancer genetics revolution has moved rapidly. The first cancer gene to be identified was BRCA1 in 1990, followed by BRCA2 in 1994. At that time, leading scientists and two commercial testing laboratories informally agreed not to offer a BRCA test to the general public, because there were many questions about the risk posed by the mutation.[1] In 1996, however, a private commercial institute begin offering the test to the public, arguing that women had the right to know whether they carry the mutated gene.[1] Other advances came with the sequencing of other high-penetrance genes, such as MLH1 and MSH2, in 2000. In 2006, the BRACAnalysis® Large Rearrangement Test (Myriad; Zurich, Switzerland) became available.

Simultaneously, scientists gained data on the cancer risks associated with various genes and strategies for managing them. A seminal study published in 2010 demonstrated that risk-reducing salpingo-oophorectomy in BRCA1/BRCA2 mutation carriers is associated with a lower risk for ovarian cancer, first diagnosis of breast cancer, all-cause mortality, breast cancer-specific mortality, and ovarian cancer-specific mortality.[2] "This study really showed the benefit of genetic testing [for cancer]," said Claudine Isaacs, MD, professor of medicine and oncology and co-director of the Fisher Center for Hereditary Cancer and Clinical Genomics Research at Georgetown University. "Before this, it really felt like we were just staring into this crystal ball and giving people bad news without any evidence for what to do to mitigate some of that risk."

Other patient management advances followed. MRI was shown to be superior to mammography or ultrasound for screening women with a BRCA1 or BRCA2 mutation.[3,4] Clinicians developed guidelines for managing patients with certain gene mutations, including individuals with hereditary diffuse gastric cancer and Lynch syndrome.[5,6] With technology evolving at warp speed, it soon became possible to offer next-generation sequencing for patients, which allowed the simultaneous testing of multiple genes.

Meanwhile, an epic court battle was being waged over whether a gene could be patented. In June 2013, the Supreme Court ruled that although naturally isolated, DNA is not patentable. "The [BRCA] patent was disallowed and multiple vendors entered the market—not just for BRCA, but also BRCA and multiple other genes," said Jeffrey Weitzel, MD, director of the Clinical Cancer Genetics Program and professor of oncology and population sciences at City of Hope in Duarte, California.

There has been an explosion of multiplex gene panels for cancer since then. "Multiplex gene panel use is increasing," said Alison Kurian, MD, MSc, who directs the Women's Cancer Genetics Clinic at Stanford University. "What we are seeing typically is testing simultaneously of 15-40 genes, instead of only a few."


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