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Serrated Neoplasia Pathway: A Clue to NTRK-Rearranged Colorectal Tumors

By: Celeste L. Dixon
Posted: Wednesday, November 24, 2021

Important novel details about the landscape of NTRK gene fusions in the context of colorectal carcinogenesis pathways have emerged from research conducted by Gyeong Hoon Kang, MD, PhD, of Seoul National University College of Medicine, and colleagues. The team used immunohistochemistry to assess pan-TRK protein in more than 1,000 retrospectively collected colorectal epithelial tumor tissues. They found that NTRK oncogenic fusions were specifically and exclusively in sessile serrated pathway–associated tumors without BRAF/KRAS mutations. These tumors and lesions included sessile serrated lesions, sessile serrated lesions with dysplasia, and MLH1-methylated microsatellite instability–high colorectal cancers. Their work was published in The Journal of Pathology.

This advancement in understanding is notable, as NTRK fusions continue to emerge as tissue-agnostic targets for oncologic agents. NTRK fusions, the team continued, “are a relatively early event that can occur morphologically prior to full dysplastic change and molecularly prior to microsatellite instability–high development in sessile serrated lesions.”

In their analysis, not a single microsatellite-stable colorectal cancer, conventional adenoma, traditional serrated adenoma, or hyperplastic polyp had TRK positivity, explained the researchers. However, Dr. Kang and co-investigators continued, TRK positivity was found in 11 of 58 (19%) MLH1-methylated microsatellite instability–high colorectal cancers, 4 of 23 (17%) sessile serrated lesions with dysplasias, and 5 of 132 (4%) sessile serrated lesions. Additionally, NTRK fusions were detected only in sessile serrated lesions of patients 50 years or older, whereas BRAF mutations were found in younger patients’ sessile serrated lesions.

Disclosure: The study authors reported no conflicts of interest.



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