Patient-specific factors influence somatic variation patterns in von Hippel–Lindau disease renal tumours

• Published in: Nature communications Vol. 7; no. 1; pp. 11588 - 9
• Main Authors: Fei, Suzanne S., Mitchell, Asia D., Heskett, Michael B., Vocke, Cathy D., Ricketts, Christopher J., Peto, Myron, Wang, Nicholas J., Sönmez, Kemal, Linehan, W. Marston, Spellman, Paul T.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 13.05.2016; Nature Publishing Group; Nature Portfolio
• Subjects: 631/208/2489/68; 631/208/737; 692/699/67/589/1588; Adult; Bias; Cancer; Carcinogens, Environmental; Carcinoma, Renal Cell - genetics; Carcinoma, Renal Cell - pathology; Carcinoma, Renal Cell - surgery; Chromosomes; Chromosomes, Human - genetics; DNA Copy Number Variations - genetics; DNA Mutational Analysis; Environmental Exposure - adverse effects; Female; Genome, Human - genetics; Genomes; Humanities and Social Sciences; Humans; Kidney Neoplasms - genetics; Kidney Neoplasms - pathology; Kidney Neoplasms - surgery; Laboratory animals; Male; Medical research; Middle Aged; multidisciplinary; Mutation; Patients; Polymorphism, Single Nucleotide - genetics; Science; Science (multidisciplinary); Tumors; von Hippel-Lindau Disease - genetics; von Hippel-Lindau Disease - pathology; von Hippel-Lindau Disease - surgery; Young Adult; Oregon; United States > US
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms11588

Cancer development is presumed to be an evolutionary process that is influenced by genetic background and environment. In laboratory animals, genetics and environment are variables that can largely be held constant. In humans, it is possible to compare independent tumours that have developed in the same patient, effectively constraining genetic and environmental variation and leaving only stochastic processes. Patients affected with von Hippel–Lindau disease are at risk of developing multiple independent clear cell renal carcinomas. Here we perform whole-genome sequencing on 40 tumours from six von Hippel-Lindau patients. We confirm that the tumours are clonally independent, having distinct somatic single-nucleotide variants. Although tumours from the same patient show many differences, within-patient patterns are discernible. Single-nucleotide substitution type rates are significantly different between patients and show biases in trinucleotide mutation context. We also observe biases in chromosome copy number aberrations. These results show that genetic background and/or environment can influence the types of mutations that occur. Analysing multiple tumours from the same patient permits the study of the germline contribution to cancer. Here, the authors sequence multiple renal tumours from VHL patients and find that intra-patient tumours are clonally distinct but share some genetic features, suggesting that patient-specific factors influence tumour formation.