American Urological Association

Copy Number Alterations in Sarcomatoid RCC Examined

Researchers at Fox Chase Cancer Center compared copy number alterations in sarcomatoid renal cell carcinoma (RCC) to those in clear cell, papillary, and chromophobe RCC to identify unique changes that might harbor genetic drivers of sarcomatoid RCC. The results were presented at the 2015 AUA Annual Meeting in New Orleans.

Tim-Ito-revTimothy Ito, MD, a surgical oncology fellow at Fox Chase, along with Joseph R. Testa, PhD, co-leader of Fox Chase’s Cancer Biology Program, and colleagues examined SNP microarrays performed on macrodissected tissue from 81 tumors; 17 had sarcomatoid differentiation. Copy number alterations present in more than 25% of the cases were deemed significant, and significant copy number alterations in sarcomatoid specimens were compared to those found in the other histologic subtypes. Sarcomatoid tumors had significantly higher numbers of copy number alterations when compared to other histologies. Copy number alterations that occurred significantly more frequently in sarcomatoid tumors included losses of chromosome arms 9q, 15q, 18p and q, and 22q, as well as gains of chromosome arms 1q and 8q.

The researchers reported that 9 of the sarcomatoid tumors arose in a background of clear cell RCC, 2 in papillary RCC, 2 in mixed clear cell and papillary RCC, and 4 in unclassified RCC. Sarcomatoid patients presented significantly more often with lymph node or distant metastatic disease, and patients with sarcomatoid tumors experienced a significantly worse overall survival. Patients with higher numbers of copy number alterations also experienced significantly worse overall survival.

Ito and colleagues concluded that sarcomatoid differentiation is associated with a high rate of chromosomal imbalances. Further examination of candidate genes on chromosome arms uniquely altered in sarcomatoid tumors may provide more insight into drivers of this aggressive phenotype.