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https://doi.org/10.14300/mnnc.2023.18034

Analysis of the function of the genes with the highest number of germinal mutations in patients with leukoplakia and cancer of the oral mucosa

[Original research] [Oncology]
Natalia Anatolievna Karpuk; Sergey Rubnikovich; Oksana Cheslavovna Mazur; Ivan Viktorovich Zhyltsov; Ivan Yurievich Karpuk; Sergey Sirak; Evgeny Shchetinin; Alena Petrovna Mikhalenko;

To date, a small fraction of the mutations associated with a high risk of developing neoplasms of the oral mucosal (OM) have been described. An important consideration is the determination of germ genetic variants related to the development of leukoplakia (LOM) and squamous cell carcinoma (SCCOM). The function of the genes with the highest number of bacterial mutations was carried out in 24 patients with LEO and 24 patients with SCCOM. It was found that the structure of the identified mutations was dominated by variants of the MUC3A, MUC4, MUC12, and MUC16 genes responsible for the synthesis of the mucin glycoprotein family (44.7 % and 41.2 % of germinal mutations in patients with LOM and SCCOM, respectively). Insufficient production or a decrease in the functional activity of mucins is a trigger factor for both the development of keratosis and malignant degeneration of epitheliocytes. An infrequent germline mutation p.K416E of the CHEK2 gene, found in 29.2 % of patients with LOM and 25 % of patients with SCCOM, is associated with the development of both diseases with a high probability (RR 822.67 in LOM and RR 705.15 in SCCOM). Thus, the obtained data contribute to developing test systems PCR and NGS to predict the course of these diseases and personalize therapy.

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References:
1. Villa A., Hanna G. J., Kacew A., Frustino J., Hammerman P. S. [et al.]. Oral keratosis of unknown significance shares genomic overlap with oral dysplasia. Oral Dis. 2019;25(7):1707-1714. https://doi.org/10.1111/odi.13155
2. Noto Z., Tomihara K., Furukawa K., Noguchi M. Dyskeratosis congenita associated with leukoplakia of the tongue. Int. J. Oral Maxillofac. surg. 2016;45(6):760-763. https://doi.org/10.1016/j.ijom.2015.12.005
3. Farah C. S., Jessri M., Bennett N. C., Dalley A. J., Shearston K. D. [et al.] Exome sequencing of oral leukoplakia and oral squamous cell carcinoma implicates DNA damage repair gene defects in malignant transformation. Oral Oncol. 2019;96:42-50. https://doi.org/10.1016/j.oraloncology.2019.07.005
4. Govindarajan G. V., Bhanumurthy L., Balasubramanian A., Ramanathan A. A Novel Mutation in the DNA Binding Domain of NFKB is Associated with Speckled Leukoplakia. Asian Pac. J. Cancer Prev. 2016;17(7):3627-3629.
5. Ogmundsdóttir H. M., Hilmarsdóttir H., Astvaldsdóttir A., Jóhannsson J. H., Holbrook W. P. Oral lichen planus has a high rate of TP53 mutations. A study of oral mucosa in icelanD. Eur. J. Oral sci. 2002;110(3):192-198. https://doi.org/10.1034/j.1600-0447.2002.21235.x
6. Kresty L. A., Mallery S. R., Knobloch T. J., Li J., Lloyd M. [et al.]. Frequent alterations of p16INK4a and p14ARF in oral proliferative verrucous leukoplakia. Cancer Epidemiol. Biomarkers Prev. 2008;17(11):3179-3187. https://doi.org/10.1158/1055-9965.EPI-08-0574
7. Han E., Patel N. A., Yannuzzi N. A. A unique case of coats plus syndrome and dyskeratosis congenita in a patient with CTC1 mutations. Ophthalmic Genet. 2020;41(4):363-367. https://doi.org/10.1080/13816810.2020.1772315
8. Mao L. NOTCH mutations: multiple faces in human malignancies. Cancer Prev. Res. (Phila). 2015;8(4):259-261. https://doi.org/10.1158/1940-6207.CAPR-15-0063
9. Gouvêa A. F., Santos Silva A. R., Speight P. M., Hunter K., Carlos R. [et al.] High incidence of DNA ploidy abnormalities and increased Mcm2 expression may predict malignant change in oral proliferative verrucous leukoplakia. Histopathology. 2013;62(4):551-562. https://doi.org/10.1111/his.12036
10. Zarate A. M., Don J., Secchi D., Carrica A., Costa F. G. [et al.] Study of the TP53 codon 72 polymorphism in oral cancer and oral potentially malignant disorders in Argentine patients. Tumor Biol. 2017;39(5):1010428317699113. https://doi.org/10.1177/1010428317699113.
11. Ribeiro I. P., Marques F., Barroso L., Rodrigues J., Caramelo F. [et al.] Genomic profile of oral squamous cell carcinomas with an adjacent leukoplakia or with an erythroleukoplakia that evolved after the treatment of primary tumor: A report of two cases. Mol. Med. Rep. 2017;16(5):6780-6786. https://doi.org/10.3892/mmr.2017.7428
12. Chang S. E., Bhatia P., Johnson N. W., Morgan P. R., McCormick F. [et al.] Ras mutations in United Kingdom examples of oral malignancies are infrequent. Int. J. Cancer. 1991;48(3):409-412. https://doi.org/10.1002/ijc.2910480318
13. Chung C. M., Hung C. C., Lee C. H., Lee C. P., Lee K. W. [et al.] Variants in FAT1 and COL9A1 genes in male population with or without substance use to assess the risk factors for oral malignancy. PLos One. 2019;14(1):e0210901. https://doi.org/10.1371/journal.pone.0210901
14. Nextera DNA Exome Reference (1000000039018). Available at: https://support.illumina.com/content/dam/illumina-support/documents/documentation/chemistry_documentation/samplepreps_nextera/nextera-dna-exome/nextera-dna-exome-reference-1000000039018-00.pdf. Accessed December 6, 2022.
15. Illumina TruSight Oncology 500 Reference Guide. Available at: https://support.illumina.com/content/dam/illumina-support/documents/documentation/chemistry_documentation/trusight/oncology-500/trusight-oncology500-reference-guide-1000000067621_07.pdf. Accessed May 5, 2022.
16. Kanzi A. M., San J. E., Chimukangara B., Wilkinson E., Fish M. [et al.] Next Generation Sequencing and Bioinformatics Analysis of Family Genetic Inheritance. Front. Genet. 2020;11:544162. https://doi.org/10.3389/fgene.2020.544162
17. Fox A. J., Hiemenz M. C., Lieberman D. B., Sukhadia S., Li B. [et al.] Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors. J. Vis. Exp. 2016;(115):52758. https://doi.org/10.3791/52758
18. Buzdugan L., Kalisch M., Navarro A., Schunk D., Fehr E., Bühlmann P. Assessing statistical significance in multivariable genome wide association analysis. Bioinformatics. 2016;32(13):1990-2000. https://doi.org/10.1093/bioinformatics/btw128
19. Reibel J. Prognosis of oral pre-malignant lesions: significance of clinical, histopathological, and molecular biological characteristics. Crit. Rev. Oral Biol. Med. 2003;14(1):47-62. https://doi.org/10.1177/154411130301400105
20. Kumar M. H., Sanjai K., Kumarswamy J., Keshavaiah R., Papaiah L. [et al.] Expression of MUC1 mucin in potentially malignant disorders, oral squamous cell carcinoma and normal oral mucosa: An immunohistochemical study. J. Oral Maxillofac. Pathol. 2016;20(2):214-218. https://doi.org/10.4103/0973-029X.185916
21. Villa A., Celentano A., Glurich I., Borgnakke W. S., Jensen S. B. [et al.] World Workshop on Oral Medicine VII: Prognostic biomarkers in oral leukoplakia: A systematic review of longitudinal studies. Oral Dis. 2019;25(Suppl 1):64-78. https://doi.org/10.1111/odi.13087
22. The Genome Aggregation Database (gnomAD). Available at: https://gnomad.broadinstitute.org. Accessed July 25, 2022.
23. Boonen R., Wiegant W. W., Celosse N., Vroling B., Heijl S. [et al.] Functional Analysis Identifies Damaging CHEK2 Missense Variants Associated with Increased Cancer Risk. Cancer Res. 2022;82(4):615-631. https://doi.org/10.1158/0008-5472.CAN-21-1845
24. Offit K., Garber J. E. Time to check CHEK2 in families with breast cancer? J. Clin. Oncol. 2008;26(4):519-520. https://doi.org/10.1200/JCO.2007.13.8503

Keywords: genes, germinal mutations, leukoplakia, cancer, oral mucosa