Biomarker NTRK Coverage from Every Angle

ESMO 2021: NTRK Fusion and KRAS Variation in Colorectal and Lung Cancers

By: Vanessa A. Carter, BS
Posted: Friday, September 24, 2021

During the European Society for Medical Oncology (ESMO) Congress 2021, Chenlu Zhang, MD, of Zhongshan Hospital, Fudan University, Shanghai, China, and colleagues presented their research on high levels of microsatellite instability and KRAS mutations in patients with colorectal cancer harboring NTRK gene fusions (Abstract 1765P). Their results showed that these genetic anomalies might not only be mutually exclusive in this type of colorectal cancer, but patients with NTRK fusions may have the potential to benefit from immune checkpoint inhibitor therapy. However, validation in a clinical trial is warranted.

From approximately 20,000 patients with solid tumors, tumor tissue and paired white blood cells were collected and analyzed. Microsatellite instability status was analyzed from 500 loci and 74 cancer-related genes.

Of the total population, 46 individuals with colorectal cancer (n = 14), lung cancer (n = 15), or other cancer types (n =17) harbored one or more NTRK fusions. Of the patients with colorectal cancer, 11 had high levels of microsatellite instability, but none exhibited a KRAS variation. Among 299 cases of colorectal cancer without NTRK fusions, however, more than half (50.17%) harbored a KRAS mutation. Mutations of TSC2 and NRAS were also detected in patients without NTRK fusions but not in those who harbored them.

The most frequently mutated genes in both NTRK fusion-positive and ­negative lung cancers were EGFR and TP53, with variations occurring at similar rates. Notably, the only gene frequently mutated in cancer types other than colorectal or lung cancer was TP53. However, key driver genes such as PIK3CA, APC, ROS1, CTNNB1, and EGFR were found in several patients.

Disclosure: The study authors reported no conflicts of interest.

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