High-throughput tissue microarray analysis of CMYC amplificationin urinary bladder cancer

Area of Science:

• Oncology
• Genetics
• Urology

Background:

• Chromosome 8 alterations, particularly 8p deletions and 8q gains, are common in bladder cancer.
• The CMYC oncogene on chromosome 8q24 is a potential driver of tumor progression.
• Limited data exists on the clinical significance of CMYC copy number alterations in bladder cancer.

Purpose of the Study:

• To investigate the impact of CMYC gene copy number alterations on tumor progression and patient prognosis in bladder cancer.
• To determine the frequency of CMYC amplifications and gains in a large cohort of bladder cancer samples.

Main Methods:

• Fluorescence in situ hybridization (FISH) was used to analyze CMYC copy number.
• A tissue microarray comprising 2317 bladder cancer samples was utilized.
• Statistical analyses were performed to correlate CMYC alterations with tumor stage, grade, and patient survival.

Main Results:

• CMYC copy number increases were associated with advanced tumor stage and high histologic grade.
• CMYC amplifications occurred in 0.6% of pTa, 4% of pT1, and 5.5% of pT2-4 tumors.
• CMYC gains were observed in 10.5% of pTa, 15.8% of pT1, and 21.4% of pT2-4 tumors.
• CMYC copy number changes did not significantly affect patient prognosis.

Conclusions:

• Alterations in CMYC gene copy number are associated with genetically unstable bladder cancers.
• These alterations correlate with high histologic grade and/or invasive tumor growth.
• CMYC copy number status does not serve as a prognostic biomarker for bladder cancer patients.