TITLE:
Computational Analysis of TP53 Mutations in Cataracts and Breast, Prostate, and Oral Cavity Cancers in Senegal
AUTHORS:
Fatimata Kane, Mame Diarra Samb, Fatimata Mbaye, Mbacke Sembene
KEYWORDS:
TP53, Somatic Mutations, Cataracts, Breast Cancer, Prostate Cancer, Oral Cavity Cancer, In Silico Analysis, Protein Structure
JOURNAL NAME:
Open Journal of Genetics,
Vol.15 No.4,
December
29,
2025
ABSTRACT: Mutations in the TP53 gene are among the most common genetic alterations in many cancers, and they are also suspected to play a role in the development of cataracts. TP53 is a tumor suppressor gene, and its alteration can dysregulate the expression of genes directly or indirectly controlled by the p53 protein. This may lead to impaired DNA damage repair, defective cell-cycle arrest, altered chromatin remodeling, and disrupted apoptosis. Cataracts, the leading cause of blindness, and cancer, the second leading cause of death worldwide, are still often diagnosed at late stages. This study aimed to evaluate the involvement of TP53 mutations in cataracts and in breast, prostate, and oral cavity cancers in Senegalese patients. A total of 116 patients were included: cataract (n = 29), oral cavity cancer (n = 33), prostate cancer (n = 15), breast cancer (n = 16), and controls (n = 23). Tissue samples were collected during biopsy after informed consent. DNA extraction, PCR amplification, and sequencing were performed. Mutation Surveyor was used to detect mutations; Mutation Taster, SIFT, and PolyPhen-2 were used to predict pathogenicity. DynaMut2 and I-Mutant were used to evaluate the impact of pathogenic variants on protein stability, and Missense3D was used to assess effects on the three-dimensional structure of p53. Cataract and oral cavity cancer tissues harbored more pathogenic variants (19 and 14, respectively) than breast and prostate cancer tissues (7 and 11, respectively). The variants c.506T > G (p. Met169Arg), c.652G > A (p. Val218Met), and c.672 + 1G > T were shared by prostate and breast cancers. The variants c.576G > C (p. Gln192His), c.642T > G (p. His214Gln), c.644G > A (p. Ser215Asn), and c.645T > G (p. Ser215Arg) were common to cataracts and oral cavity cancers. Structural analysis using Missense3D showed that some mutations caused no detectable structural damage, whereas significant conformational alterations were observed at codons 175 and 196 (variants c.524G > C and c.587G > C). These findings suggest that TP53 mutations may occur early in the development of cataract as well as in oral cavity, breast, and prostate cancers. This study provides baseline molecular data that could contribute to improving early detection and clinical management of these diseases in Senegalese patients.