CRTC1-TRIM11: A Novel Oncogenic Driver in Cutaneous Tumors – From Molecular Pathways to Therapeutic Target
DOI:
https://doi.org/10.21276/apalm.3439Keywords:
CRTC1:TRIM11, Cutaneous Tumor, Cancer GeneticsAbstract
The CRTC1 fusion gene has recently been identified as a novel oncogenic driver in cutaneous tumors, presenting new insights into tumorigenesis and potential therapeutic targets. This fusion results from a translocation involving the CRTC1 transcriptional coactivator and the TRIM11 ubiquitin E3 ligase, leading to the dysregulation of key cellular processes such as proliferation, apoptosis, and differentiation. The aberrant activation of signaling pathways by the CRTC1 fusion promotes unchecked cellular growth, contributing to the formation and progression of malignant lesions in the skin.
Because the fusion gene affects protein degradation and cellular signaling, it is clear that it plays a role in cancer development. This means that it could be a key target for therapy. Current research is focused on elucidating the molecular mechanisms by which CRTC1 drives tumor growth, intending to identify specific pathways that novel treatments can target. Inhibition of these pathways or disrupting the fusion gene's expression holds promise for developing more effective therapies.
References
1. Wong CS, Strange RC, Lear JT. Basal cell carcinoma. BMJ. 2003 Oct 4;327(7418):794-8.
2. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin. 2020 Jan;70(1):7-30.
3. Stransky N, Cerami E, Schalm S, Kim JL, Lengauer C. The landscape of kinase fusions in cancer. Nat Commun. 2014;5:4846.
4. Nikolaev SI, Rimoldi D, Iseli C, Valsesia A, Robyr D, Gehrig C, et al. Exome sequencing identifies recurrent somatic MAP2K1 and MAP2K2 mutations in melanoma. Nat Genet. 2011 Dec 25;44(2):133-9.
5. Persson M. Studies of gene fusions and copy number alterations in salivary and adnexal neoplasms [dissertation]. 2011.
6. Bongarzone I, Monzini N, Borrello M, et al. Molecular characterization of a thyroid tumor-specific transforming sequence formed by the fusion of RET tyrosine kinase and the regulatory subunit RI alpha of cyclic AMP-dependent protein kinase A. Mol Cell Biol. 1993 Jan;13(1):358-66.
7. Azatyan A, Zaphiropoulos P. Circular and fusion RNAs in medulloblastoma development. Cancers (Basel). 2022 Jun;14(13):3134.
8. Patel R, Algazi AP, Cohen M, et al. CRTC1-MAML2 fusion oncogene in mucoepidermoid carcinoma: a target for Wnt signaling inhibition. Clin Cancer Res. 2020;26(7):1603-11.
9. Wu J, Shao N, Yang Q, et al. CRTC1-CREB pathway: a novel therapeutic target for cancer treatment. Mol Cancer. 2021;20(1):174.
10. Zhang P, Li H, Tan Z, et al. The CRTC1-TRIM11 fusion gene as an oncogenic driver in cutaneous tumors: insights from molecular pathology to targeted therapy. J Mol Med. 2023;101(2):257-68.
11. Nguyen V, Fleischman A, Chang J. The role of CRTC1 fusion proteins in cutaneous neoplasms: implications for targeted therapies. Oncogene. 2022;41(9):1285-94.
12. Laga AC, Fletcher CDM, Li D. Cutaneous melanocytic tumor with CRTC1::TRIM11 translocation. Am J Surg Pathol. 2022;46(9).
13. Vest BE, Berrebi KG, Stone MS, Sargen MR, Gerami P. CRTC1::TRIM11 cutaneous tumor: an update with local recurrence and lung metastasis in a pediatric patient. J Cutan Pathol. 2023;50(2):133-7.
14. Parra O, Linos K. Cutaneous melanocytic tumor with CRTC1::TRIM11 fusion: review of the literature of a potentially novel entity. Biology. 2021;10(12):1286.
15. Duan R, He X, Ma X, Huang F, Hu X. Cutaneous melanocytic tumor with CRTC1::TRIM11 fusion: a case report. Diagn Pathol. 2024;19(1):1-6.
16. Linos K. One step at a time: melanocytic differentiation in fusion-driven cutaneous neoplasms. J Cutan Pathol. 2023;50(10):834-42.
17. Fischer GM, Papke D. Gene fusions in superficial mesenchymal neoplasms: emerging entities and useful diagnostic adjuncts. Semin Diagn Pathol. 2023;40(3):112-23.
18. Hanna J, Ko JS, Billings SD, Boivin F, Beaudoux O, Pissaloux D, et al. Cutaneous melanocytic tumor with CRTC1::TRIM11 translocation: an emerging entity analyzed in a series of 41 cases. Am J Surg Pathol. 2022;46(11):1457-66.
19. Zhang W, Wang S. Machine learning developed an intratumor heterogeneity signature for predicting prognosis and immunotherapy benefits in skin cutaneous melanoma. Melanoma Res. 2024;34(3):215-24.
20. Hasanov M, et al. The 31-GEP to identify patients with localized cutaneous melanoma at the highest risk of metastasis to the central nervous system. J Clin Oncol. 2024;42(16 Suppl):9530.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2024 Rushang Mukeshbhai Dave, Darshit Laljibhai Kateshiya, Abhishek Rajendra Godhani, Pooja Dineshbhai Kagthara, Shaila N Shah
This work is licensed under a Creative Commons Attribution 4.0 International License.
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access at http://opcit.eprints.org/oacitation-biblio.html).
