Colon cancer in a patient with a mosaic monoallelic germline pathogenic NF1 gene variant
TL;DR
This case highlights the co-occurrence of an NF1 variant and dMMR colorectal cancer and underscores the need for further studies to determine whether this represents a coincidental finding or a biologically meaningful association.
Abstract
Pathogenic variants in the tumor suppressor gene NF1 cause neurofibromatosis type 1 (NF1), one of the most common hereditary cancer predisposition syndromes. Pathogenic NF1 variants have been associated with an increased risk of several cancers; however, the relationship between NF1 variation and colon cancer remains underreported. We report a 41-year-old woman with a mosaic monoallelic germline pathogenic NF1 variant, NM_000267.3:c.1756_1759del (p.Thr586Valfs*18), previously detected on germline multigene panel testing in saliva at a variant allele frequency of approximately 35%. She later presented with fatigue, dyspnea on exertion, and iron-deficiency anemia. Computed tomography, colonoscopy, biopsy, mismatch repair immunohistochemistry, surgical pathology, and tumor next-generation sequencing led to the diagnosis of right-sided colon adenocarcinoma that was mismatch repair deficient (dMMR) and microsatellite instability-high (MSI-H). She underwent right hemicolectomy, recovered postoperatively, and entered standard surveillance; at the time of manuscript development, she was also receiving systemic therapy. This case highlights the co-occurrence of an NF1 variant and dMMR colorectal cancer and underscores the need for further studies to determine whether this represents a coincidental finding or a biologically meaningful association.