Identification of somatic mutations and their effects in a Thai population with both non-muscle invasive and muscle invasive bladder cancer using whole exome sequencing analysis
DOI:
https://doi.org/10.52786/isu.a.101Keywords:
Urothelial carcinoma, non-muscle invasive bladder cancer, muscle invasive bladder cancer, somatic mutation, whole exome sequencingAbstract
Objective: Whole exome sequencing is a new technology which enables the detection of genetic mutation in cancer. Genetic alterations in urothelial carcinoma have been identified and studies are being carried out with regard to clinical applications. Proposals have been made pertinent to molecular classifications for the prediction of treatment response and prognosis. To date, there is a paucity of data regarding somatic mutation of bladder cancer in Thailand, therefore, the aim of this study is to identify specific somatic mutations associated with different types of bladder cancer in Thailand.
Materials and Methods: Fourteen patients were enrolled onto this study, 7 with non-muscle invasive (NMIBC) and 7 with muscle invasive bladder cancer (MIBC). DNA was isolated from peripheral blood mononuclear cells and tumor tissue for whole exome sequencing to identify any tumor somatic mutations and the mutation burden in each patient. The results were analyzed and correlated with the clinical status of the patients after treatment.
Results: In the NMIBC group, the most common mutated genes were found to be HLA-F, KDM6A, and TTN. In the MIBC group, the most common mutated genes were TP53, TTN, and KMT2D. Patients with urothelial carcinoma with small cell variant show TP53 and RB1 mutation. This is the same as the current consensus on molecular classification. The disease has usually metastasized after 1 year. This supports the evidence that Neuroendocrine-like groups have poorer prognosis.
Conclusion: The somatic mutations of bladder cancer in this Thai population showed greater diversity of genetic alteration in comparison with the worldwide database. The mutations in the muscle invasive bladder cancer were the same as previous findings. We also found a similar association in neuroendocrine-like genomic mutations. Despite the number of patients in this study being small, there is evidence of genetic diversity and tumor origins of mutation in our patients.
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