Reza Mehrazin1, Essel Dulaimi2, Robert G Uzzo3, Karthik Devarjan4, Jianming Pei2, Marc C Smaldone3, Alexander Kutikov3, Joseph R Testa2, Tahseen Al-Saleem2. 1. Department of Urology and Oncological Science, Icahn School of Medicine at Mount Sinai, New York, NY, USA. 2. Divisions of Pathology and Cancer Biology, Fox Chase Cancer Center-Temple Health System, Philadelphia, PA, USA. 3. Divisions of Urologic Oncology, Fox Chase Cancer Center-Temple Health System, Philadelphia, PA, USA. 4. Divisions of Biostatistics; Fox Chase Cancer Center-Temple Health System, Philadelphia, PA, USA.
Abstract
BACKGROUND: The proto-oncogene c-MYC, located on chromosome 8q, can be upregulated through gain of 8q, causing alteration in biology of renal cell carcinoma (RCC). The aim of this study was to evaluate the prevalence of c-MYC through chromosome 8q gain and to correlate findings with cancer-specific mortality (CSM), and overall survival (OS). METHODS: Cytogenetic analysis by conventional or Chromosomal Genomic Microarray Analysis (CMA) was performed on 414 renal tumors. Nonclear and nonpapillary RCC were excluded. Impact of gain in chromosome 8q status on CSM, OS, and its correlation with clinicopathological variables were evaluated. CSM and OS were assessed using log-rank test and the Cox proportional hazards model. RESULTS: A total of 297 RCC tumors with cytogenetic analysis were included. Gain of 8q was detected in 18 (6.1%) tumors (9 clear cell and 9 papillary RCC), using conventional method (n = 11) or CMA (n = 7). Gain of 8q was associated with higher T stage (p < 0.001), grade (p < 0.001), nodal involvement (p = 0.005), and distant metastasis (p < 0.001). No association between gain of 8q and age (p = 0.23), sex (p = 0.46), and Charlson comorbidity index (CCI, p = 0.59) were seen. Gain of 8q was associated with an 8.38-fold [95% confidence interval (CI), 3.83-18.34, p < 0.001] and 3.31-fold (95% CI, 1.56-7.04, p = 0.001) increase in CSM and decrease in OS, respectively, at a median follow up of 56 months. CONCLUSION: Chromosome 8q harbors the proto-oncogene c-MYC, which can be upregulated by gain of 8q. Our findings suggest that gain of 8q, can predict aggressive tumor phenotype and inferior survival in RCC.
BACKGROUND: The proto-oncogene c-MYC, located on chromosome 8q, can be upregulated through gain of 8q, causing alteration in biology of renal cell carcinoma (RCC). The aim of this study was to evaluate the prevalence of c-MYC through chromosome 8q gain and to correlate findings with cancer-specific mortality (CSM), and overall survival (OS). METHODS: Cytogenetic analysis by conventional or Chromosomal Genomic Microarray Analysis (CMA) was performed on 414 renal tumors. Nonclear and nonpapillary RCC were excluded. Impact of gain in chromosome 8q status on CSM, OS, and its correlation with clinicopathological variables were evaluated. CSM and OS were assessed using log-rank test and the Cox proportional hazards model. RESULTS: A total of 297 RCC tumors with cytogenetic analysis were included. Gain of 8q was detected in 18 (6.1%) tumors (9 clear cell and 9 papillary RCC), using conventional method (n = 11) or CMA (n = 7). Gain of 8q was associated with higher T stage (p < 0.001), grade (p < 0.001), nodal involvement (p = 0.005), and distant metastasis (p < 0.001). No association between gain of 8q and age (p = 0.23), sex (p = 0.46), and Charlson comorbidity index (CCI, p = 0.59) were seen. Gain of 8q was associated with an 8.38-fold [95% confidence interval (CI), 3.83-18.34, p < 0.001] and 3.31-fold (95% CI, 1.56-7.04, p = 0.001) increase in CSM and decrease in OS, respectively, at a median follow up of 56 months. CONCLUSION: Chromosome 8q harbors the proto-oncogene c-MYC, which can be upregulated by gain of 8q. Our findings suggest that gain of 8q, can predict aggressive tumor phenotype and inferior survival in RCC.
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