Presentation Authors: Julian Marcon*, Alejandro Sanchez, Sounak Gupta, Renzo G. Di Natale, Amar Sandhu, Roy Mano, Andrew W. Silagy, Kyle A. Blum, Daniel E. Nassau, Robert J. Motzer, Jonathan A. Coleman, Paul Russo, Victor E. Reuter, A. Ari Hakimi, Eduard Reznik, New York, NY
Introduction: Translocation renal cell carcinoma (tRCC) is a rare kidney neoplasm, however, in patients under 45 years the incidence is up to 15%. Recent studies provided first insights into the genomic underpinnings of tRCC, but additional cohorts are required to fully understand the molecular evolution of these tumors. We performed allele-specific copy-number (ASCN) analysis on next-generation sequencing (NGS) data to further investigate the genomic evolution of tRCC.
Methods: We identified 42 patients with tRCC between 1997 and 2017. Diagnosis of tRCC was confirmed with positive immunohistochemistry and/or FISH results. The sequencing cohort consisted of 27 patients. Whole-exome sequencing was performed in 13 of the samples, 14 were sequenced with our institutional panel (MSK-IMPACTÂ®). We performed somatic variant calling and ASCN analysis using our bioinformatics pipeline. To infer the relative timing of oncogenic events, we computed clonality estimates, using the purity and ploidy estimates from the copy-number variation (CNV) analysis. Clinical correlates were evaluated using non-parametric hypothesis tests. Survival estimates were produced using the Kaplan-Meier method.
Results: Of the sequencing cohort, a total of 11 men and 11 women had comprehensive mutation and copy-number information. Six patients presented with metastatic disease (22%). The median age was 42.5 years (IQR 33-52); this value was used to stratify patients into old and young groups. The median follow-up time was 27.3 months. The frequent somatic events and translocation binding partners are illustrated in Fig.1a, the frequencies of copy-number events are shown in Fig.1b. Patients older than 42.5 years showed a higher burden of TERT mutations (p=0.21) and an increased rate of CNVs (p=0.11), however, these results were not significant. Overall survival was worse for patients with 9p-loss (p=0.032). The time to recurrence was shorter in patients with 3p-loss (p=0.009) or 15q-loss (p=0.0027). Also, there was a significant association between 4q-loss and metastatic disease at presentation (p=0.009).
Conclusions: Our data suggests that the genomic landscape of tRCC may vary according to the age at diagnosis. Additional oncogenic events in older patients may drive a more aggressive phenotype. Somatic CNVs seem to play an important role in patient prognosis.
Source of Funding: This research was funded in part through the NIH/NCI Cancer Center Support Grant P30 CA008748. Ruth L. Kirschstein Research Service Award T32CA082088 (AS).