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Review
. 2023 Aug;143(8):1369-1377.
doi: 10.1016/j.jid.2022.12.027. Epub 2023 Jun 15.

Cutaneous Neurofibroma Heterogeneity: Factors that Influence Tumor Burden in Neurofibromatosis Type 1

Chunhui Jiang  1 , Renée M McKay  1 , Sang Y Lee  2 , Carlos G Romo  2 , Jaishri O Blakeley  2 , Muzlifah Haniffa  3 , Eduard Serra  4 , Matthew R Steensma  5 , David Largaespada  6 , Lu Q Le  7
Affiliations
Review

Cutaneous Neurofibroma Heterogeneity: Factors that Influence Tumor Burden in Neurofibromatosis Type 1

Chunhui Jiang et al. J Invest Dermatol. 2023 Aug.

Abstract

Neurofibromatosis type 1 is one of the most common genetic disorders of the nervous system and predisposes patients to develop benign and malignant tumors. Cutaneous neurofibromas (cNFs) are NF1-associated benign tumors that affect nearly 100% of patients with NF1. cNFs dramatically reduce patients' QOL owing to their unaesthetic appearance, physical discomfort, and corresponding psychological burden. There is currently no effective drug therapy option, and treatment is restricted to surgical removal. One of the greatest hurdles for cNF management is the variability of clinical expressivity in NF1, resulting in intrapatient and interpatient cNF tumor burden heterogeneity, that is, the variability in the presentation and evolution of these tumors. There is growing evidence that a wide array of factors are involved in the regulation of cNF heterogeneity. Understanding the mechanisms underlying this heterogeneity of cNF at the molecular, cellular, and environmental levels can facilitate the development of innovative and personalized treatment regimens.

Keywords: ECM; GEM; KO; LOH; MAPK/extracellular signal–regulated kinase kinase; MEK; MPNST; NF1; cNF; cutaneous neurofibroma; extracellular matrix; genetically engineered mouse; knockout; loss of heterozygosity; malignant peripheral nerve sheath tumor; neurofibromatosis type 1; pNF; plexiform neurofibroma.

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Conflict of interest statement

CONFLICT OF INTEREST

DL is on the board of directors of and a scientific advisor to Recombinetics, a gene editing company whose work is described in the paper. JOB, ES, MRS, LQL, SYL and CGR receive support from the Neurofibromatosis Therapeutic Acceleration Progam (NTAP) at Johns Hopkins University. LQL, MRS, and JOB receive funding from the Department of Defense. JOB is a consultant for SpringWorks Therapeutics. The remaining authors state no conflict of interest.

Figures

Figure 1.
Figure 1.. Cutaneous neurofibroma burden in patients with NF1 varies widely.
Shown are clinical pictures of cutaneous neurofibromas showing the range of disease burden, which can be just a few to many hundreds or even thousands. The subjects consented to the publication of the images. NF1, neurofibromatosis type 1.
Figure 2.
Figure 2.. Cells of origin in the Schwann cell lineage, together with intrinsic and extrinsic factors, give rise to neurofibroma.
(a) Diagram showing the life of cutaneous neurofibroma starting from Schwann cell lineage maturation. (b) Diagram showing the roles of the tumor microenvironment (extrinsic factors) that impact neurofibroma development. Image was created with BioRender.com. BC, boundary cap; CALM, café-au-lait macule; cNF, cutaneous neurofibroma; DRG, dorsal root ganglion; LOH, loss of heterozygosity; MC, melanocyte; NCSC, neural crest stem cell; pNF, plexiform neurofibroma; SC, Schwann cell.
See this image and copyright information in PMC

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