Exploration of Neuroscience

Table 1. Clinical timeline of diagnostic workup, treatment, and follow-up.

Clinical period	Key events	Verified findings/management
Approximately 2 years before colon cancer diagnosis	Germline multigene testing performed because of hearing loss, scoliosis, and developmental delay	Mosaic monoallelic pathogenic NF1 variant NM_000267.3:c.1756_1759del (p.Thr586Valfs*18) identified in saliva at variant allele frequency (VAF) ~35%; Lynch syndrome-associated germline variants not detected
Presentation period	Evaluation of fatigue, dyspnea on exertion, and anemia	Symptoms prompted gastrointestinal workup for occult blood loss and structural lesion
Diagnostic workup	Imaging, colonoscopy, biopsy, mismatch repair immunohistochemistry, and tumor sequencing	Obstructing proximal ascending colon tumor identified; biopsy confirmed adenocarcinoma; dMMR/MSI-H tumor profile established
Definitive local treatment	Right hemicolectomy	Two foci of invasive adenocarcinoma (3.5 cm and 4.0 cm), well differentiated with mucinous features; staged as T3 N0 and T2 N0 (stage II)
Postoperative course and follow-up	Recovery and surveillance	Recovered postoperatively and followed per standard surveillance protocol; systemic therapy was ongoing at manuscript development

Return to article view

Declarations

Author contributions

FA: Conceptualization, Investigation, Writing—original draft, Writing—review & editing. KMC: Methodology, Writing—review & editing. MG: Methodology, Writing—review & editing. EH: Methodology, Writing—review & editing. MBA: Methodology, Writing—review & editing. DBV: Methodology, Writing—review & editing. MBS: Methodology, Writing—review & editing. MAO: Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Resources, Supervision, Validation, Writing—review & editing. All authors read and approved the submitted version.

Conflicts of interest

The authors declare that they have no conflicts of interest.

Ethical approval

This study was deemed to be exempt from review by the Mayo Clinic Institutional Review Board. This case was carried out in compliance with the Declaration of Helsinki.

Consent to participate

Informed consent to participate in the study was obtained from all participants.

Consent to publication

Informed consent to publication was obtained from relevant participants.

Availability of data and materials

The data supporting the findings of this case report are available from the corresponding author upon reasonable request.

Funding

This study was funded by a grant from the Children’s Tumor Foundation (Grant ID: 2023-04-003). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Copyright

Publisher’s note

Open Exploration maintains a neutral stance on jurisdictional claims in published institutional affiliations and maps. All opinions expressed in this article are the personal views of the author(s) and do not represent the stance of the editorial team or the publisher.

References

Safonov A, Nomakuchi TT, Chao E, Horton C, Dolinsky JS, Yussuf A, et al. A genotype-first approach identifies high incidence of NF1 pathogenic variants with distinct disease associations. Nat Commun. 2025;16:3121. [DOI] [PubMed] [PMC]

Wallace MR, Marchuk DA, Andersen LB, Letcher R, Odeh HM, Saulino AM, et al. Type 1 Neurofibromatosis Gene: Identification of a Large Transcript Disrupted in Three NF1 Patients. Science. 1990;249:181–6. [DOI] [PubMed]

Lee TJ, Chopra M, Kim RH, Parkin PC, Barnett-Tapia C. Incidence and prevalence of neurofibromatosis type 1 and 2: a systematic review and meta-analysis. Orphanet J Rare Dis. 2023;18:292. [DOI] [PubMed] [PMC]

Yap YS, McPherson JR, Ong CK, Rozen SG, Teh BT, Lee AS, et al. The NF1 gene revisited—from bench to bedside. Oncotarget. 2014;5:5873–92. [DOI] [PubMed] [PMC]

Dasgupta B, Dugan LL, Gutmann DH. The Neurofibromatosis 1 Gene Product Neurofibromin Regulates Pituitary Adenylate Cyclase-Activating Polypeptide-Mediated Signaling in Astrocytes. J Neurosci. 2003;23:8949–54. [DOI] [PubMed] [PMC]

Koczkowska M, Callens T, Chen Y, Gomes A, Hicks AD, Sharp A, et al. Clinical spectrum of individuals with pathogenic NF1 missense variants affecting p.Met1149, p.Arg1276, and p.Lys1423: genotype–phenotype study in neurofibromatosis type 1. Hum Mutat. 2020;41:299–315. [DOI] [PubMed] [PMC]

Mantalovas S, Karakousis VA, Sevva C, Roulia P, Savvakis S, Anthimidis G, et al. 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. Cancers. 2025;17:1934. [DOI] [PubMed] [PMC]

Ibrahimi A, Lachkar S, Boualaoui I, El Sayegh H, Nouini Y. Gastrointestinal stromal tumor in patient with neurofibromatosis type 1: A case report. Int J Surg Case Rep. 2025;129:111166. [DOI] [PubMed] [PMC]

Cerrah E, Çomunoğlu C. 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. Int J Surg Pathol. 2024;32:1415–21. [DOI] [PubMed]

10.

Deshpande A, Munoz J, Dabak V, Hanbali A, Kurzrock R. Images in Immunotherapy and Precision Oncology: A Case Report of Neurofibromatosis-1. J Immunother Precis Oncol. 2024;7:122–5. [DOI] [PubMed] [PMC]

11.

Morgan E, Arnold M, Gini A, Lorenzoni V, Cabasag CJ, Laversanne M, et al. Global burden of colorectal cancer in 2020 and 2040: incidence and mortality estimates from GLOBOCAN. Gut. 2022;72:338–44. [DOI] [PubMed]

12.

Siegel RL, Giaquinto AN, Jemal A. Cancer statistics, 2024. CA: Cancer J Clin. 2024;74:12–49. [DOI] [PubMed]

13.

Eng C, Yoshino T, Ruiz-García E, Mostafa N, Cann CG, O'Brian B, et al. Colorectal cancer. Lancet. 2024;404:294–310. [DOI] [PubMed]

14.

Storandt MH, Sinicrope FA. Deficient mismatch repair/microsatellite instability-high colorectal cancer: current treatment paradigms, limitations and future perspectives. BMJ Oncol. 2026;5:e000980. [DOI] [PubMed] [PMC]

15.

Taieb J, Svrcek M, Cohen R, Basile D, Tougeron D, Phelip JM. Deficient mismatch repair/microsatellite unstable colorectal cancer: Diagnosis, prognosis and treatment. Eur J Cancer. 2022;175:136–57. [DOI] [PubMed]

16.

Lou H, Zhai C, Gong L, Pan H, Pan H, Zhang Y, et al. NF1 germline mutation in a Chinese family with colon cancer. J Int Med Res. 2020;48:300060519896435. [DOI] [PubMed] [PMC]

17.

Oh SH, Lee JH, Namgung H. A Case of Rectal Cancer in a Patient with Neurofibromatosis Type 1. J Korean Soc Coloproctology. 2012;28:170–3. [DOI] [PubMed] [PMC]

18.

Gagnier JJ, Kienle G, Altman DG, Moher D, Sox H, Riley D, et al. The CARE guidelines: consensus-based clinical case reporting guideline development. BMJ Case Rep. 2013;2013:bcr2013201554. [DOI] [PubMed] [PMC]

19.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, et al. Sherloc: a comprehensive refinement of the ACMG–AMP variant classification criteria. Genet Med. 2017;19:1105–17. [DOI] [PubMed] [PMC]

20.

Eroglu S, Birsenogul I, Bowen AP, Doyle JF, Pupkin SE, Villar J, et al. Lynch Syndrome in Focus: A Multidisciplinary Review of Cancer Risk, Clinical Management, and Special Populations. Cancers. 2025;17:3981. [DOI] [PubMed] [PMC]

21.

Gómez-Molina R, Martínez R, Suárez M, Peña-Cabia A, Calderón MC, Mateo J. Lynch syndrome and colorectal cancer: A review of current perspectives in molecular genetics and clinical strategies. Oncol Res. 2025;33:1531–45. [DOI] [PubMed] [PMC]

22.

Oliver TRW, Lawson ARJ, Lee-Six H, Tollit A, Jung H, Hooks Y, et al. Cancer-independent somatic mutation of the wild-type NF1 allele in normal tissues in neurofibromatosis type 1. Nat Genet. 2025;57:515–21. [DOI] [PubMed] [PMC]

23.

Nguyen LH, Goel A, Chung DC. Pathways of Colorectal Carcinogenesis. Gastroenterology. 2020;158:291–302. [DOI] [PubMed] [PMC]

24.

Chan WY, Pires da Silva I, Long GV, Rizos H. Targeting MEK in cancer and beyond: mechanistic insights and therapeutic opportunities. Lancet. 2026;407:1639–56. [DOI] [PubMed]

25.

Suppiah S, Mansouri S, Bril V, Zadeh G. Special issue: a contemporary landscape of the clinical and biological research in neurofibromatosis type 1. Neurooncol Adv. 2020;2:i8–12. [DOI] [PubMed] [PMC]

26.

Anastasaki C, Woo AS, Messiaen LM, Gutmann DH. Elucidating the impact of neurofibromatosis-1 germline mutations on neurofibromin function and dopamine-based learning. Hum Mol Genet. 2015;24:3518–28. [DOI] [PubMed] [PMC]

27.

Bhamidipati D, Subbiah V. Tumor-agnostic drug development in dMMR/MSI-H solid tumors. Trends Cancer. 2023;9:828–839. [DOI] [PubMed]

28.

Ferner RE, Huson SM, Thomas N, Moss C, Willshaw H, Evans DG, et al. Guidelines for the diagnosis and management of individuals with neurofibromatosis 1. J Med Genet. 2006;44:81–8. [DOI] [PubMed] [PMC]

29.

Carton C, Evans DG, Blanco I, Friedrich RE, Ferner RE, Farschtschi S, et al. ERN GENTURIS tumour surveillance guidelines for individuals with neurofibromatosis type 1. eClinicalMedicine. 2023;56:101818. [DOI] [PubMed] [PMC]

30.

Benson AB, Venook AP, Adam M, Chang G, Chen YJ, Ciombor KK, et al. Colon Cancer, Version 3.2024, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Cancer Netw. 2024;22:e22. [DOI] [PubMed]

31.

Saqi IK, Nielsen AT, Madsen MT, Gögenur I, Orhan A, Justesen TF. Tumor characteristics impact prognosis in deficient mismatch repair/microsatellite instability-high localized colorectal cancer—a systematic review and meta-analysis. JNCI Cancer Spectr. 2025;10:e10. [DOI] [PubMed] [PMC]

32.

Kim JH, Kang GH. Molecular and prognostic heterogeneity of microsatellite-unstable colorectal cancer. World J Gastroenterol. 2014;20:4230–43. [DOI] [PubMed] [PMC]