Genomic characterization of sarcomatoid transformation in clear cell renal cell carcinoma.
نویسندگان
چکیده
The presence of sarcomatoid features in clear cell renal cell carcinoma (ccRCC) confers a poor prognosis and is of unknown pathogenesis. We performed exome sequencing of matched normal-carcinomatous-sarcomatoid specimens from 21 subjects. Two tumors had hypermutation consistent with mismatch repair deficiency. In the remainder, sarcomatoid and carcinomatous elements shared 42% of somatic single-nucleotide variants (SSNVs). Sarcomatoid elements had a higher overall SSNV burden (mean 90 vs. 63 SSNVs, P = 4.0 × 10(-4)), increased frequency of nonsynonymous SSNVs in Pan-Cancer genes (mean 1.4 vs. 0.26, P = 0.002), and increased frequency of loss of heterozygosity (LOH) across the genome (median 913 vs. 460 Mb in LOH, P < 0.05), with significant recurrent LOH on chromosomes 1p, 9, 10, 14, 17p, 18, and 22. The most frequent SSNVs shared by carcinomatous and sarcomatoid elements were in known ccRCC genes including von Hippel-Lindau tumor suppressor (VHL), polybromo 1 (PBRM1), SET domain containing 2 (SETD2), phosphatase and tensin homolog (PTEN). Most interestingly, sarcomatoid elements acquired biallelic tumor protein p53 (TP53) mutations in 32% of tumors (P = 5.47 × 10(-17)); TP53 mutations were absent in carcinomatous elements in nonhypermutated tumors and rare in previously studied ccRCCs. Mutations in known cancer drivers AT-rich interaction domain 1A (ARID1A) and BRCA1 associated protein 1 (BAP1) were significantly mutated in sarcomatoid elements and were mutually exclusive with TP53 and each other. These findings provide evidence that sarcomatoid elements arise from dedifferentiation of carcinomatous ccRCCs and implicate specific genes in this process. These findings have implications for the treatment of patients with these poor-prognosis cancers.
منابع مشابه
Sarcomatoid Chromophobe Renal Cell Carcinoma with Heterologous Component
Clear cellrenal cell carcinoma (RCC) is the most common malignant renal tumor in adults, while chromophobe RCC (CRCC) is the third most common. Any subtypes of RCC can undergo sarcomatoid differentiation, but heterologous differentiation in sarcomatoid area is very rare in RCC. Here a61-year male is presented with hematuria and palpable mass. Clinicoradiologically, RCC was considered and left r...
متن کاملSarcomatoid Carcinoma of Renal Pelvis Involving Ureter and Renal Parenchyma with Heterologous Osteosarcomatous Differentiation: A Case Report and Review of Literature
Sarcomatoid carcinoma is a high‑grade rare malignant tumor with both epithelial and mesenchymal components. Sarcomatoid carcinoma in the upper urinary tract is very rare. We reported here a case of sarcomatoid carcinoma of renal pelvis with osteosarcomatous differentiation, with involvement of the ureter and renal parenchyma in a 68-year-old female. Histologically, predominant pleomorphic spind...
متن کاملBiphasic components of sarcomatoid clear cell renal cell carcinomas are molecularly similar to each other, but distinct from, non‐sarcomatoid renal carcinomas
Sarcomatoid transformation, wherein an epithelioid carcinomatous tumour component coexists with a sarcomatoid histology, is a predictor of poor prognosis in clear cell renal cell carcinoma. Our understanding of sarcomatoid change has been hindered by the lack of molecular examination. Thus, we sought to characterize molecularly the biphasic epithelioid and sarcomatoid components of sarcomatoid ...
متن کاملMetastatic Renal cell Carcinoma Presenting as a clear-cell Tumor in Tongue: A Case Report
Introduction: Metastatic lesions of the oral cavity are extremely rare, accounting for approximately 1% of all malignant oral tumors. The most common primary sources of metastatic tumors in the oral region are, from the most to the least common, the breast, lung, kidney, bone, and colon. Renal cell carcinoma accounts for nearly 3% of all adult malignancies. It usually metastasizes to the lungs,...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- Proceedings of the National Academy of Sciences of the United States of America
دوره 113 8 شماره
صفحات -
تاریخ انتشار 2016