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Comparative Lesions Analysis Through a Targeted Sequencing Approach
Published on: November 5, 2019
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Targeted hotspot profiling reveals a functionally relevant mutation in bladder cancer
Md Naiem Hossain1, Depro Das2, Munshi Akid Mostofa3
1Nutritional, Genes and Human Disease Laboratory, Department of Biochemistry and Molecular Biology, University of Dhaka, Dhaka, Bangladesh.
Urologic Oncology
|September 10, 2025
Summary
This study identified STK11 mutations as key drivers in Bangladeshi bladder cancer. These genetic alterations impact tumor suppressor function, potentially affecting patient prognosis and cancer progression.
Area of Science:
- Genomics
- Cancer Biology
- Molecular Oncology
Background:
- Understanding cancer's mutational landscape is crucial for identifying progression mechanisms.
- This study profiles somatic mutations in Bangladeshi bladder cancer patients to reveal underlying genetic alterations.
Purpose of the Study:
- To profile somatic mutations in bladder cancer patients from Bangladesh.
- To investigate the genetic alterations driving bladder cancer in this population.
- To identify key mutations and their functional impact on tumor progression.
Main Methods:
- Targeted sequencing of 50 oncogenes and tumor suppressor genes.
- Somatic variant identification using GATK Mutect2 and annotation with ANNOVAR.
- Molecular subtyping via NMF clustering and ssGSEA; protein modeling and molecular dynamics simulations for functional impact assessment.
Main Results:
- Frameshift indels and missense SNVs were prevalent, with high mutation rates in ATM, APC, STK11, TP53, and others.
- A deleterious STK11 mutation (F255S) destabilized the protein, reduced ATP binding affinity, and impaired kinase function, suggesting loss of tumor suppressive activity.
- Two molecular subtypes (basal and luminal) were identified; the basal subtype showed increased immune infiltration and aggressive traits despite lower tumor mutational burden.
Conclusions:
- STK11 mutations are significant in Bangladeshi bladder cancer, impacting tumor progression.
- The identified molecular subtypes offer potential prognostic and therapeutic stratification avenues.
- This research provides insights into the genetic basis of bladder cancer in a specific demographic.
