The genomic and epigenomic evolutionary history of papillary renal cell carcinomas
Wedge, David C
AffiliationDivision of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD, 20892, USA.
MetadataShow full item record
AbstractIntratumor heterogeneity (ITH) and tumor evolution have been well described for clear cell renal cell carcinomas (ccRCC), but they are less studied for other kidney cancer subtypes. Here we investigate ITH and clonal evolution of papillary renal cell carcinoma (pRCC) and rarer kidney cancer subtypes, integrating whole-genome sequencing and DNA methylation data. In 29 tumors, up to 10 samples from the center to the periphery of each tumor, and metastatic samples in 2 cases, enable phylogenetic analysis of spatial features of clonal expansion, which shows congruent patterns of genomic and epigenomic evolution. In contrast to previous studies of ccRCC, in pRCC, driver gene mutations and most arm-level somatic copy number alterations (SCNAs) are clonal. These findings suggest that a single biopsy would be sufficient to identify the important genetic drivers and that targeting large-scale SCNAs may improve pRCC treatment, which is currently poor. While type 1 pRCC displays near absence of structural variants (SVs), the more aggressive type 2 pRCC and the rarer subtypes have numerous SVs, which should be pursued for prognostic significance.
CitationZhu B, Poeta ML, Costantini M, Zhang T, Shi J, Sentinelli S, et al. The genomic and epigenomic evolutionary history of papillary renal cell carcinomas. Nat Commun. 2020;11(1):3096.
- Characterization of Clinical Cases of Advanced Papillary Renal Cell Carcinoma via Comprehensive Genomic Profiling.
- Authors: Pal SK, Ali SM, Yakirevich E, Geynisman DM, Karam JA, Elvin JA, Frampton GM, Huang X, Lin DI, Rosenzweig M, Lipson D, Stephens PJ, Ross JS, Miller VA, Agarwal N, Shuch B, Choueiri TK, Chung JH
- Issue date: 2018 Jan
- In silico DNA methylation analysis identifies potential prognostic biomarkers in type 2 papillary renal cell carcinoma.
- Authors: Yang M, Hlady RA, Zhou D, Ho TH, Robertson KD
- Issue date: 2019 Sep
- Distinct Genomic Copy Number Alterations Distinguish Mucinous Tubular and Spindle Cell Carcinoma of the Kidney From Papillary Renal Cell Carcinoma With Overlapping Histologic Features.
- Authors: Ren Q, Wang L, Al-Ahmadie HA, Fine SW, Gopalan A, Sirintrapun SJ, Tickoo SK, Reuter VE, Chen YB
- Issue date: 2018 Jun
- Clonal architectures predict clinical outcome in clear cell renal cell carcinoma.
- Authors: Huang Y, Wang J, Jia P, Li X, Pei G, Wang C, Fang X, Zhao Z, Cai Z, Yi X, Wu S, Zhang B
- Issue date: 2019 Mar 18
- Genomic profiling of renal cell carcinoma in patients with end-stage renal disease.
- Authors: Inoue T, Matsuura K, Yoshimoto T, Nguyen LT, Tsukamoto Y, Nakada C, Hijiya N, Narimatsu T, Nomura T, Sato F, Nagashima Y, Kashima K, Hatakeyama S, Ohyama C, Numakura K, Habuchi T, Nakagawa M, Seto M, Mimata H, Moriyama M
- Issue date: 2012 Mar