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SUO 2018

SUO 2018: Clinicopathologic Correlates of Copy Number Variations in Clear Cell Renal Cell Carcinoma: A Study of 178 Samples Profiled with Next-generation Sequencing

Phoenix, Arizona (UroToday.com) Renal cell carcinoma (RCC) was once viewed as a single and distinct solid organ malignancy, but is now understood to represent a diverse group of tumors arising from a common source. Contemporary sequencing studies have shed light on a diverse group of cancers with varying genetic blue prints. It has been previously reported that copy number variations in clear cell RCC (ccRCC), particularly loss of chromosome arm 9p and 14q, are associated with worse oncologic outcomes. A comprehensive study of all possible arm-level copy-number changes has not been previously published using next-generation sequencing, and the authors of this study aimed to study associations between the occurrence of these events and various cancer outcomes.

Angela Yoo reviewed sequenced cases of ccRCC contained in the institutional sequencing program at Memorial Sloan-Kettering Cancer Center (MSK-IMPACT). The group performed allele-specific copy-number analyses using validated bioinformatics tools. They focused on “broad arm-level events,” examining segments with the highest fraction of each chromosomal arm. They then performed analyses to determine recurrence-free survival rates.

A total of 178 samples remained after exclusion criteria were applied. The authors found that loss of 9p (p<0.001) and 14q (p=0.008) were both associated with shorter time to recurrence in univariate analyses; findings from a multivariate analysis were not reported. Furthermore, they demonstrated that when loss of 9p was present, it was associated with concurrent loss of 9q in the majority of patients (97%, p< 0.001), supporting that loss of segments in chromosome 9 usually results in complete chromosomal loss. They additionally found that loss of 9p was associated with loss of 14q in 78% of cases (p<0.001), suggesting that the two chromosomal losses are interlinked. Regression analyses were performed to explore associations of chromosomal losses with oncologic outcomes, and the authors found that 9p loss was associated with metastatic disease (OR 4 95% CI 1.6-10.2), larger primary (OR 7.9 95% CI 1.7-37.8) and higher stage (T3) (OR 3.6 95% CI 1.2-11.2). The wide confidence intervals are likely due to the relatively limited sample size, but the findings are nonetheless significant.

Yoo concluded that after evaluating all possible arm-level changes in copy-number of all chromosome arms, 9p and 14q were found to be statistically significant, correlated, and associated with worse oncologic outcomes. Her study highlights the future role of genomics in prognostication of outcomes in renal cell carcinoma.

Presented By: Marc A. Dall’Era, MD, University of California, Davis

Written by: Selma Masic, MD, Society of Urologic Oncology Fellow, Fox Chase Cancer Center, Philadelphia, PA, at the 19th Annual Meeting of the Society of Urologic Oncology (SUO), November 28-30, 2018 – Phoenix, Arizona