The somatic genomic landscape of chromophobe renal cell carcinoma

By Caleb F. Davis, C. Ricketts, Min Wang, Lixing Yang, A. Cherniack, Hui Shen, C. Buhay, Hyojin Kang, Sang Cheol Kim, Catherine C Fahey and 36 more. Cancer Cell, 2014

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Summary We describe the landscape of somatic genomic alterations of 66 chromophobe renal cell carcinomas (ChRCCs) based on multidimensional and comprehensive characterization, including mitochondrial DNA (mtDNA) and whole genome sequencing. The result is consistent that ChRCC originates from the distal nephron compared to other kidney cancers with more proximal origins. Combined mtDNA and gene expression analysis implicates changes in mitochondrial function as a component of the disease biology, while suggesting alternative roles for mtDNA mutations in cancers relying on oxidative phosphorylation. Genomic rearrangements lead to recurrent structural breakpoints within TERT promoter region, which correlates with highly elevated TERT expression and manifestation of kataegis, representing a mechanism of TERT up-regulation in cancer distinct from previously-observed amplifications and point mutations.

Subfields: Cancer Research, Genetics, Pulmonary and Respiratory Medicine

View Paper: https://www.semanticscholar.org/paper/671155d8c1547c7a8159e675b031c78dd61ff8e4

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Citations in the corpus

Oncogenic Signaling Pathways in The Cancer Genome Atlas (2018, background): “…al., 2013; Cancer Genome Atlas Network, 2012a, 2012b, 2015a, 2015b, Cancer Genome Atlas Research Network, 2008, 2011, 2013a, 2013b, 2014a, 2014b, 2014c, 2014d, 2017a, 2017b; Davis et al., 2014), each of which included the pathway genes found to be genetically altered in the individual tumor types.”
Renal cell carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. (2010, background): “ Some patients with chromophobe RCC may benefit from mTOR inhibitors since mutation on chromosome 7 was shown to lead to a loss of the folliculin gene with upregulation of mTOR [9].”
FACETS: allele-specific copy number and clonal heterogeneity analysis tool for high-throughput DNA sequencing (2016, methodology): “Figure 2 shows FACETS analysis of a TCGA chromophobe renal cell carcinoma (chRCC) sample (TCGA-KL-8331), revealing multiple chromosomal losses including chromosomes 1, 2, 6, 10, 13, 17, 21 which are signatures of chRCC genome alteration as characterized in the TCGA chRCC study (11).”
The Cancer Genome Atlas Comprehensive Molecular Characterization of Renal Cell Carcinoma (2018, methodology): “Mitochondrial (mt) DNA mutation analysis, which was previously performed only in ChRCC (Davis et al., 2014), was conducted in a representative number of tumors from all RCC subtypes.”
Renal cell carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up†. (2019, background): “ Some patients with chromophobe RCC may benefit from mTOR inhibitors since mutation on chromosome 7 was shown to lead to a loss of the folliculin gene with upregulation of mTOR [9].”
Renal cell carcinoma (2017, background): “As we begin to appreciate the impact that prevalent RCC mutations (in PBRM1, SETD2, BAP1, KDM5C, PTEN, and TP53) have on clinical outcomes, incorporating specific mutational information into prognostic nomograms will become increasingly useful.”
Cell-of-Origin Patterns Dominate the Molecular Classification of 10,000 Tumors from 33 Types of Cancer (2018, background): “Pan-kidney mapped almost entirely to C28, except for KICH, which grouped with ACC in C9, characterized by a high frequency of hypodiploid samples (Davis et al., 2014; Zheng et al., 2016).”