Evidence of mutations in tumour suppressor genes among oral cancer in Naswar, smokeless tobacco users
Objective: Smokeless tobacco has been linked to the genetic modification of oral squamous cell carcinoma (OSCC). Our study aims to further investigate the disease among Naswar users at the genomic level to understand genetic diversity and discover new targeted therapy. Methods: A multi-centre des...
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Medical Journals Sweden
2025-06-01
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| Series: | Acta Odontologica Scandinavica |
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| Online Access: | https://medicaljournalssweden.se/actaodontologica/article/view/43778 |
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| author | Fatima Iqbal Sajjad Ahmad Hoor Maryam Humaira Amin |
| author_facet | Fatima Iqbal Sajjad Ahmad Hoor Maryam Humaira Amin |
| author_sort | Fatima Iqbal |
| collection | DOAJ |
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Objective: Smokeless tobacco has been linked to the genetic modification of oral squamous cell carcinoma (OSCC). Our study aims to further investigate the disease among Naswar users at the genomic level to understand genetic diversity and discover new targeted therapy.
Methods: A multi-centre descriptive cross sectional research was designed comprising a total of 80 cases of OSCC who were habitual users of Naswar. Out of the 80 cases, whole exome sequencing (WES) was applied to 7 formalin fixed paraffin embedded (FFPE) tissues of OSCC. We further investigated immunohistochemical expression of mutant TP53 and CDKN2A protein in tissues of 80 OSCC samples. Statistical analysis was performed using the Statistical Package for Social Sciences (SPSS) version 19.
Results: Among the total 2,216 somatic variants identified in tumour suppressor genes (TSGs), we compared the high frequency mutation genes reported in OSCC in Catalogue of Somatic Mutations in Cancer (COSMIC) database with research samples, and found that TP53 (85.7%), NOTCH1 (85.7%), and FAT1 (85.7%) showed higher rate of mutation. Among single nucleotide variants, higher prevalence of C/T and G/A base change was noted. Interestingly, a distinct panel of 12 genes was detected to be mutated in 100% samples which was not previously reported compared to Single Nucleotide Polymorphism Database (dbSNP). PTPRT mutation (rs2867655) was present in seven samples and IGF2R (rs629849) was seen in two samples. A statistically significant relation was observed between mutant TP53 protein expression and duration of Naswar use and clinical stages while difference in CDKN2A protein expression was found to be statistically significant with respect to stage only.
Conclusions: Our study presented preliminary data of genetic aberrations in patients exposed to known risk factor (Naswar). These findings can enhance the understanding of genetic aetiology and serve as basis for innovative targets of therapy.
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| format | Article |
| id | doaj-art-9b87baee3ce843899dc5121dc9f55b83 |
| institution | OA Journals |
| issn | 0001-6357 1502-3850 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Medical Journals Sweden |
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| series | Acta Odontologica Scandinavica |
| spelling | doaj-art-9b87baee3ce843899dc5121dc9f55b832025-08-20T02:05:23ZengMedical Journals SwedenActa Odontologica Scandinavica0001-63571502-38502025-06-018410.2340/aos.v84.43778Evidence of mutations in tumour suppressor genes among oral cancer in Naswar, smokeless tobacco usersFatima Iqbal0Sajjad Ahmad1Hoor Maryam 2Humaira Amin3Faculty of Health & Medical Sciences, Riphah International University, Islamabad, PakistanFaculty of Health & Medical Sciences, Riphah International University, Islamabad, PakistanFaculty of Health & Medical Sciences, Riphah International University, Islamabad, PakistanDepartment of Genomics and Bioinformatics, Cholistan University of Veterinary and Animal Sciences, Bahawalpur Objective: Smokeless tobacco has been linked to the genetic modification of oral squamous cell carcinoma (OSCC). Our study aims to further investigate the disease among Naswar users at the genomic level to understand genetic diversity and discover new targeted therapy. Methods: A multi-centre descriptive cross sectional research was designed comprising a total of 80 cases of OSCC who were habitual users of Naswar. Out of the 80 cases, whole exome sequencing (WES) was applied to 7 formalin fixed paraffin embedded (FFPE) tissues of OSCC. We further investigated immunohistochemical expression of mutant TP53 and CDKN2A protein in tissues of 80 OSCC samples. Statistical analysis was performed using the Statistical Package for Social Sciences (SPSS) version 19. Results: Among the total 2,216 somatic variants identified in tumour suppressor genes (TSGs), we compared the high frequency mutation genes reported in OSCC in Catalogue of Somatic Mutations in Cancer (COSMIC) database with research samples, and found that TP53 (85.7%), NOTCH1 (85.7%), and FAT1 (85.7%) showed higher rate of mutation. Among single nucleotide variants, higher prevalence of C/T and G/A base change was noted. Interestingly, a distinct panel of 12 genes was detected to be mutated in 100% samples which was not previously reported compared to Single Nucleotide Polymorphism Database (dbSNP). PTPRT mutation (rs2867655) was present in seven samples and IGF2R (rs629849) was seen in two samples. A statistically significant relation was observed between mutant TP53 protein expression and duration of Naswar use and clinical stages while difference in CDKN2A protein expression was found to be statistically significant with respect to stage only. Conclusions: Our study presented preliminary data of genetic aberrations in patients exposed to known risk factor (Naswar). These findings can enhance the understanding of genetic aetiology and serve as basis for innovative targets of therapy. https://medicaljournalssweden.se/actaodontologica/article/view/43778Oral squamous cell carcinomatumour suppressor geneswhole exome sequencingmutationstargeted therapy |
| spellingShingle | Fatima Iqbal Sajjad Ahmad Hoor Maryam Humaira Amin Evidence of mutations in tumour suppressor genes among oral cancer in Naswar, smokeless tobacco users Acta Odontologica Scandinavica Oral squamous cell carcinoma tumour suppressor genes whole exome sequencing mutations targeted therapy |
| title | Evidence of mutations in tumour suppressor genes among oral cancer in Naswar, smokeless tobacco users |
| title_full | Evidence of mutations in tumour suppressor genes among oral cancer in Naswar, smokeless tobacco users |
| title_fullStr | Evidence of mutations in tumour suppressor genes among oral cancer in Naswar, smokeless tobacco users |
| title_full_unstemmed | Evidence of mutations in tumour suppressor genes among oral cancer in Naswar, smokeless tobacco users |
| title_short | Evidence of mutations in tumour suppressor genes among oral cancer in Naswar, smokeless tobacco users |
| title_sort | evidence of mutations in tumour suppressor genes among oral cancer in naswar smokeless tobacco users |
| topic | Oral squamous cell carcinoma tumour suppressor genes whole exome sequencing mutations targeted therapy |
| url | https://medicaljournalssweden.se/actaodontologica/article/view/43778 |
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