Genetics and epigenetics of bladder cancer

Genetics and mutations in urinary bladder neoplasms Introduction: Urinary bladder neoplasms is a most common malignancy in women and the fourth common in men. And it is one of the most mortal cancer, it has distinct gene expression singular. Little is known about the genetic factors influencing bladder cancer ,although altered expression of genes related to cell cycle transcription and cytoskeleton in bladder cancer is well characterized and the mechanism of abnormal gene expression in bladder cancer remain largely obscure. According to previous research somatic and germline promotor mutations have been identified in several genes and their effect on gene expression changed have been confirmed and previous studies show that the main promotor mutation can contribute to the etiology of bladder cancer . The core promotor controls the initiation of transcription hypothesizing that mutations in the core promotor abnormality can cause abnormal transcription initiation and thus altered gene expression in bladder cancer . Finally this study was conducted to investigate the effect of genes and mutations on urinary bladder neoplasms (MIBC , NMIBC). Bladder cancer belongs to the high mutations burden cancers due to the genetic alternations in DNA repair systems that is characterized by mutations of FGFR۳ ,HER-۲ and HRAS. The result of examining ۱۶۰ patients (۸۴.۷%) NMIBC and ۴۷(۱۵.۳%) MIBC patients was that most frequently mutated gene in NMIBC was FGFR۳ (۵۳%) mutated and in NMIBC tumors was TP۵۳ (۶۰%) mutated, ۸۷% of samples mutated was in histone/chromatin. T۱ tumors showed the highest frequency of mutations in genes and transcription factor pathway (۴۵.۶%) while MIBC had the highest frequency of cell cycle. Non-silent KDMGA mutations were significantly more common in females (in T۱) compared to males . Methods: Search strategy: we searched though electronic medical data base including pubmed and web of science ,from their inception until ۱۸ september ۲۰۲۴ with no language restriction . Mesh terms: "Urinary Bladder Neoplasms"[Mesh]) AND "Genetics"[Mesh]) AND "Mutation"[Mesh]) AND "Genes"[Mesh]) AND "Gene Expression"[Mesh]) AND "Oncogenes"[Mesh]. Results: Exone and whole genome sequencing of MIBC reveal important insights into the molecular landscape but there are a few studies of NMIBC with detailed risk factor information. Conclusion: These studies show the contribution of genetic factors to the risk of bladder cancer. The core promotor mutations and another mutations mentioned in the result section can contribute to the etiology of bladder cancer. In case of early detection , mutations sensitive to chemotherapy and inhibits such as farnesyl transferase can be targeted for treatment.

کلیدواژه ها:

Genes ، Mutations ، Gene expression ، Bladder cancer ، Oncogenes