{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T08:15:57Z","timestamp":1788423357606,"version":"build-2803163510"},"reference-count":32,"publisher":"Open Exploration Publishing","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Explor Neurosci"],"accepted":{"date-parts":[[2026,8,2]]},"abstract":"<jats:p xml:lang=\"en\">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.<\/jats:p>","DOI":"10.37349\/en.2026.1006148","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T06:22:16Z","timestamp":1788416536000},"update-policy":"https:\/\/doi.org\/10.37349\/open_exploration_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Colon cancer in a patient with a mosaic monoallelic germline pathogenic NF1 gene variant"],"prefix":"10.37349","volume":"5","author":[{"given":"Feras","family":"Alsabagh","sequence":"first","affiliation":[{"name":"CLS Health Comprehensive Care Clinic\u2014Clear Lake, Webster, TX 77598, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karam M.","family":"Chaaban","sequence":"additional","affiliation":[{"name":"Department of Clinical Genomics, Mayo Clinic, Phoenix, AZ 85054, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marlene","family":"Girardo","sequence":"additional","affiliation":[{"name":"Department of Health Sciences Research, Mayo Clinic Arizona, Scottsdale, AZ 85259, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ehab","family":"Harahsheh","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mayo Clinic, Phoenix, AZ 85054, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Misha B.","family":"Asif","sequence":"additional","affiliation":[{"name":"Department of Clinical Genomics, Mayo Clinic, Phoenix, AZ 85054, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dusica","family":"Babovic-Vuksanovic","sequence":"additional","affiliation":[{"name":"Department of Clinical Genomics, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamad Bassam","family":"Sonbol","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Mayo Clinic Cancer Center, Mayo Clinic, Phoenix, AZ 85054, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6658-3964","authenticated-orcid":false,"given":"Mayowa A.","family":"Osundiji","sequence":"additional","affiliation":[{"name":"Department of Clinical Genomics, Mayo Clinic, Phoenix, AZ 85054, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"21850","published-online":{"date-parts":[[2026,9,3]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-57077-1","article-title":"A genotype-first approach identifies high incidence of NF1 pathogenic variants with distinct disease associations","volume":"16","author":"Safonov","year":"2025","journal-title":"Nat Commun"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1126\/science.2134734","article-title":"Type 1 Neurofibromatosis Gene: Identification of a Large Transcript Disrupted in Three NF1 Patients","volume":"249","author":"Wallace","year":"1990","journal-title":"Science"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-023-02911-2","article-title":"Incidence and prevalence of neurofibromatosis type 1 and 2: a systematic review and meta-analysis","volume":"18","author":"Lee","year":"2023","journal-title":"Orphanet J Rare Dis"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"5873","DOI":"10.18632\/oncotarget.2194","article-title":"The","volume":"5","author":"Yap","year":"2014","journal-title":"Oncotarget"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"8949","DOI":"10.1523\/jneurosci.23-26-08949.2003","article-title":"The Neurofibromatosis 1 Gene Product Neurofibromin Regulates Pituitary Adenylate Cyclase-Activating Polypeptide-Mediated Signaling in Astrocytes","volume":"23","author":"Dasgupta","year":"2003","journal-title":"J Neurosci"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1002\/humu.23929","article-title":"Clinical spectrum of individuals with pathogenic NF1 missense variants affecting p.Met1149, p.Arg1276, and p.Lys1423: genotype\u2013phenotype study in neurofibromatosis type 1","volume":"41","author":"Koczkowska","year":"2020","journal-title":"Hum Mutat"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.3390\/cancers17121934","article-title":"Multifocal Gastrointestinal Stromal Tumors (GISTs) of the Small Intestine in Patients with Neurofibromatosis Type 1 (NF-1): Meta-Analysis and Systematic Review of the Literature","volume":"17","author":"Mantalovas","year":"2025","journal-title":"Cancers"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijscr.2025.111166","article-title":"Gastrointestinal stromal tumor in patient with neurofibromatosis type 1: A case report","volume":"129","author":"Ibrahimi","year":"2025","journal-title":"Int J Surg Case Rep"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"1415","DOI":"10.1177\/10668969241229350","article-title":"Multiple Gastrointestinal Stromal Tumors, Malignant Peripheral Nerve Sheath Tumor and Atypical Neurofibromatous Neoplasm With Uncertain Biologic Potential Developing in A Single Patient With Neurofibromatosis Type 1 Syndrome","volume":"32","author":"Cerrah","year":"2024","journal-title":"Int J Surg Pathol"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"122","DOI":"10.36401\/jipo-23-32","article-title":"Images in Immunotherapy and Precision Oncology: A Case Report of Neurofibromatosis-1","volume":"7","author":"Deshpande","year":"2024","journal-title":"J Immunother Precis Oncol"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"338","DOI":"10.1136\/gutjnl-2022-327736","article-title":"Global burden of colorectal cancer in 2020 and 2040: incidence and mortality estimates from GLOBOCAN","volume":"72","author":"Morgan","year":"2022","journal-title":"Gut"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"12","DOI":"10.3322\/caac.21820","article-title":"Cancer statistics, 2024","volume":"74","author":"Siegel","year":"2024","journal-title":"CA: Cancer J Clin"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1016\/s0140-6736(24)00360-x","article-title":"Colorectal cancer","volume":"404","author":"Eng","year":"2024","journal-title":"Lancet"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1136\/bmjonc-2025-000980","article-title":"Deficient mismatch repair\/microsatellite instability-high colorectal cancer: current treatment paradigms, limitations and future perspectives","volume":"5","author":"Storandt","year":"2026","journal-title":"BMJ Oncol"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1016\/j.ejca.2022.07.020","article-title":"Deficient mismatch repair\/microsatellite unstable colorectal cancer: Diagnosis, prognosis and treatment","volume":"175","author":"Taieb","year":"2022","journal-title":"Eur J Cancer"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1177\/0300060519896435","volume":"48","author":"Lou","year":"2020","journal-title":"J Int Med Res"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"170","DOI":"10.3393\/jksc.2012.28.3.170","article-title":"A Case of Rectal Cancer in a Patient with Neurofibromatosis Type 1","volume":"28","author":"Oh","year":"2012","journal-title":"J Korean Soc Coloproctology"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1136\/bcr-2013-201554","article-title":"The CARE guidelines: consensus-based clinical case reporting guideline development","volume":"2013","author":"Gagnier","year":"2013","journal-title":"BMJ Case Rep"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"1105","DOI":"10.1038\/gim.2017.37","article-title":"Sherloc: a comprehensive refinement of the ACMG\u2013AMP variant classification criteria","volume":"19","author":"Nykamp","year":"2017","journal-title":"Genet Med"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.3390\/cancers17243981","article-title":"Lynch Syndrome in Focus: A Multidisciplinary Review of Cancer Risk, Clinical Management, and Special Populations","volume":"17","author":"Eroglu","year":"2025","journal-title":"Cancers"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"1531","DOI":"10.32604\/or.2025.063951","article-title":"Lynch syndrome and colorectal cancer: A review of current perspectives in molecular genetics and clinical strategies","volume":"33","author":"G\u00f3mez-Molina","year":"2025","journal-title":"Oncol Res"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"515","DOI":"10.1038\/s41588-025-02097-2","article-title":"Cancer-independent somatic mutation of the wild-type NF1 allele in normal tissues in neurofibromatosis type 1","volume":"57","author":"Oliver","year":"2025","journal-title":"Nat Genet"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1053\/j.gastro.2019.08.059","article-title":"Pathways of Colorectal Carcinogenesis","volume":"158","author":"Nguyen","year":"2020","journal-title":"Gastroenterology"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"1639","DOI":"10.1016\/s0140-6736(26)00199-6","article-title":"Targeting MEK in cancer and beyond: mechanistic insights and therapeutic opportunities","volume":"407","author":"Chan","year":"2026","journal-title":"Lancet"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"i8","DOI":"10.1093\/noajnl\/vdaa045","article-title":"Special issue: a contemporary landscape of the clinical and biological research in neurofibromatosis type 1","volume":"2","author":"Suppiah","year":"2020","journal-title":"Neurooncol Adv"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"3518","DOI":"10.1093\/hmg\/ddv103","article-title":"Elucidating the impact of neurofibromatosis-1 germline mutations on neurofibromin function and dopamine-based learning","volume":"24","author":"Anastasaki","year":"2015","journal-title":"Hum Mol Genet"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"828","DOI":"10.1016\/j.trecan.2023.07.002","article-title":"Tumor-agnostic drug development in dMMR\/MSI-H solid tumors","volume":"9","author":"Bhamidipati","year":"2023","journal-title":"Trends Cancer"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1136\/jmg.2006.045906","article-title":"Guidelines for the diagnosis and management of individuals with neurofibromatosis 1","volume":"44","author":"Ferner","year":"2006","journal-title":"J Med Genet"},{"key":"ref29","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2022.101818","article-title":"ERN GENTURIS tumour surveillance guidelines for individuals with neurofibromatosis type 1","volume":"56","author":"Carton","year":"2023","journal-title":"eClinicalMedicine"},{"key":"ref30","doi-asserted-by":"publisher","DOI":"10.6004\/jnccn.2024.0029","article-title":"Colon Cancer, Version 3.2024, NCCN Clinical Practice Guidelines in Oncology","volume":"22","author":"Benson","year":"2024","journal-title":"J Natl Compr Cancer Netw"},{"key":"ref31","doi-asserted-by":"publisher","DOI":"10.1093\/jncics\/pkaf114","article-title":"Tumor characteristics impact prognosis in deficient mismatch repair\/microsatellite instability-high localized colorectal cancer\u2014a systematic review and meta-analysis","volume":"10","author":"Saqi","year":"2025","journal-title":"JNCI Cancer Spectr"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"4230","DOI":"10.3748\/wjg.v20.i15.4230","article-title":"Molecular and prognostic heterogeneity of microsatellite-unstable colorectal cancer","volume":"20","author":"Kim","year":"2014","journal-title":"World J Gastroenterol"}],"container-title":["Exploration of Neuroscience"],"original-title":[],"language":"en","deposited":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T07:59:13Z","timestamp":1788422353000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.explorationpub.com\/Journals\/en\/Article\/1006148"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,3]]},"references-count":32,"URL":"https:\/\/doi.org\/10.37349\/en.2026.1006148","archive":["Portico","Portico"],"relation":{},"ISSN":["2834-5347"],"issn-type":[{"value":"2834-5347","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,3]]},"assertion":[{"value":"2026-04-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-02","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-03","order":2,"name":"published","label":"Published Online","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"1006148"}}