{"title":"在纳斯瓦尔，无烟烟草使用者口腔癌肿瘤抑制基因突变的证据。","authors":"Fatima Iqbal, Sajjad Ahmad, Hoor Maryam, Humaira Amin","doi":"10.2340/aos.v84.43778","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":7313,"journal":{"name":"Acta Odontologica Scandinavica","volume":"84 ","pages":"299-309"},"PeriodicalIF":1.4000,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12147670/pdf/","citationCount":"0","resultStr":"{\"title\":\"Evidence of mutations in tumour suppressor genes among oral cancer in Naswar, smokeless tobacco users.\",\"authors\":\"Fatima Iqbal, Sajjad Ahmad, Hoor Maryam, Humaira Amin\",\"doi\":\"10.2340/aos.v84.43778\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>\",\"PeriodicalId\":7313,\"journal\":{\"name\":\"Acta Odontologica Scandinavica\",\"volume\":\"84 \",\"pages\":\"299-309\"},\"PeriodicalIF\":1.4000,\"publicationDate\":\"2025-06-03\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12147670/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Acta Odontologica Scandinavica\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.2340/aos.v84.43778\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"DENTISTRY, ORAL SURGERY & MEDICINE\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Acta Odontologica Scandinavica","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2340/aos.v84.43778","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"DENTISTRY, ORAL SURGERY & MEDICINE","Score":null,"Total":0}
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 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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