Abstract:
BACKGROUND:The genomic features underpinning renal cell carcinoma with sarcomatoid dedifferentiation (sRCC) are not well understood, and at present, there are no specific or effective therapies for sRCC. OBJECTIVE:To identify genomic alterations in patients with sRCC. DESIGN, SETTING, AND PARTICIPANTS:We conducted genomic profiling on paired epithelial and sarcomatoid areas of three sRCC cases. Genomic profiling was performed on another 23 sRCC patients harboring diverse epithelial components (total of 26 cases). Genomic profiling was conducted using a hybrid capture DNA next-generation sequencing assay of 236 cancer-related genes plus 19 genes frequently rearranged in cancer. Results were compared with 56 similarly sequenced cases of clear cell RCC (ccRCC) devoid of a sarcomatoid component, and with clear cell, papillary, and chromophobe renal cell carcinoma datasets from The Cancer Genome Atlas. Four additional ccRCC cases underwent whole exome sequencing. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:Genomic alterations in patients with sRCC and ccRCC were described, and their frequencies were compared using the Fisher exact test. RESULTS AND LIMITATIONS:Two of three patients with sRCC who underwent genomic profiling of both their epithelial and sarcomatoid components demonstrated identical mutational profiles, and a third case demonstrated commonly disrupted genes. Of the 26 sRCCs, TP53 (42.3%), VHL (34.6%), CDKN2A (26.9%), and NF2 (19.2%) were the most frequently altered genes. NF2 mutations were mutually exclusive with TP53 but not with VHL mutations. Limitations include the small sample size. CONCLUSIONS:We found that sRCC contains different driver mutations than ccRCC. The epithelial and sarcomatoid components of sRCC largely contain the same genomic features. On the basis of harboring either TP53 or NF2 mutations, sRCC can be divided into two groups. These findings may have implications for understanding the oncogenesis of sarcomatoid renal tumors and for defining systemic treatment options. PATIENT SUMMARY:Next-generation sequencing of tumors from patients with sarcomatoid kidney cancer reveals mutations that differ from those in nonsarcomatoid patients. These findings have implications in understanding the pathobiology of sarcomatoid kidney cancer and indicate the need for a different treatment approach in these patients.
journal_name
Eur Uroljournal_title
European urologyauthors
Malouf GG,Ali SM,Wang K,Balasubramanian S,Ross JS,Miller VA,Stephens PJ,Khayat D,Pal SK,Su X,Sircar K,Tamboli P,Jonasch E,Tannir NM,Wood CG,Karam JAdoi
10.1016/j.eururo.2016.01.051subject
Has Abstractpub_date
2016-08-01 00:00:00pages
348-57issue
2eissn
0302-2838issn
1873-7560pii
S0302-2838(16)00170-6journal_volume
70pub_type
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