The Spectrum of Copy Number Variations in Bladder Cancer - Expert Commentary

Copy number variations (CNV) are key molecular events in the development of bladder cancer and have a prognostic value. Several studies characterized the CNVs in the genomic DNA from primary bladder tumors. However, little is known about how the CNV profiles of primary tumors compare to serum and lymph node (LN) metastasis.

A recent study by Soave et al., published in Scientific Reports, analyzed CNVs of 16 cancer-associated genes in tumor tissue, serum, and LN metastasis from 43 bladder cancer patients. The investigators used multiplex ligation-dependent probe amplification (MLPA), which is a semi-quantitative technique for determining the relative CNV in multiplex PCR. All included patients were treated with radical cystectomy and bilateral pelvic lymphadenectomy without neoadjuvant chemotherapy.

CNVs were identified in the primary tumor from 35 (83%) patients, compared to 26 (68%) and 8 (42%) patients in serum and lymph node metastasis, respectively. The most frequent CNVs were MYC, CCND1, ERBB2, and CCNE1 amplifications.

The investigators examined the association of CNVs with clinicopathologic features of bladder cancer patients. It was evident that ERBB2 CNVs were associated with variant histology and more advanced pathologic staging which are associated with aggression. CNVs in both ERBB2 and TOP2A were associated with shorter recurrence-free survival. Patients with no identified CNV in the primary tumor, compared to either serum or LN metastasis, showed a significant difference in cancer-specific and overall survival.

The observation that CNVs are more commonly identified in the primary tumor than LN metastasis and serum suggests that CNVs are early events in disease. Overall, the identified CNVs are potential targets for selecting patients for more intensive treatments at an early stage. Further studies with longitudinal sampling from serum and metastatic sites using other next-generation sequencing-based assays would provide valuable insights that build on the current observations of this study.

Written by: Bishoy M. Faltas, MD, Director of Bladder Cancer Research, Englander Institute for Precision Medicine, Weill Cornell Medicine, New York City, New York


  1. Soave A, Kluwe L, Yu H, Rink M, Gild P, Vetterlein MW, et al. Copy number variations in primary tumor, serum and lymph node metastasis of bladder cancer patients treated with radical cystectomy. Sci Rep. 2020;10(1):1–13. PMID: 33298978

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