title: Patient-specific factors influence somatic variation patterns in von Hippel-Lindau disease renal tumours.
abstract: 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.
authors.affiliation: Department of Molecular &Medical Genetics, Oregon Health &Science University, Mail Code: CL6S, 2730 SW Moody St, Portland, Oregon 97201, USA.
authors.forename: Suzanne S
authors.initials: SS
authors.lastname: Fei
authors.affiliation: Department of Molecular &Medical Genetics, Oregon Health &Science University, Mail Code: CL6S, 2730 SW Moody St, Portland, Oregon 97201, USA.
authors.forename: Asia D
authors.initials: AD
authors.lastname: Mitchell
authors.affiliation: Department of Molecular &Medical Genetics, Oregon Health &Science University, Mail Code: CL6S, 2730 SW Moody St, Portland, Oregon 97201, USA.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Heskett
authors.affiliation: Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, Building 10 Room 1-5940, Bethesda, Maryland 20892, USA.
authors.forename: Cathy D
authors.initials: CD
authors.lastname: Vocke
authors.affiliation: Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, Building 10 Room 1-5940, Bethesda, Maryland 20892, USA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Ricketts
authors.affiliation: Department of Molecular &Medical Genetics, Oregon Health &Science University, Mail Code: CL6S, 2730 SW Moody St, Portland, Oregon 97201, USA.
authors.forename: Myron
authors.initials: M
authors.lastname: Peto
authors.affiliation: Department of Biomedical Engineering, Oregon Health &Science University, Mail Code: CH13B, Portland, Oregon 97201, USA.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Wang
authors.affiliation: Department of Biomedical Engineering, Oregon Health &Science University, Mail Code: CH13B, Portland, Oregon 97201, USA.
authors.forename: Kemal
authors.initials: K
authors.lastname: Sönmez
authors.affiliation: Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, Building 10 Room 1-5940, Bethesda, Maryland 20892, USA.
authors.forename: W Marston
authors.initials: WM
authors.lastname: Linehan
authors.affiliation: Department of Molecular &Medical Genetics, Oregon Health &Science University, Mail Code: CL6S, 2730 SW Moody St, Portland, Oregon 97201, USA.
authors.forename: Paul T
authors.initials: PT
authors.lastname: Spellman
mesh_terms: D000328:Adult; D002274:Carcinogens, Environmental; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D002877:Chromosomes, Human / Q000235:genetics; D056915:DNA Copy Number Variations / Q000235:genetics; D004252:DNA Mutational Analysis; D004781:Environmental Exposure / Q000009:adverse effects*; D005260:Female; D015894:Genome, Human / Q000235:genetics; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D055815:Young Adult; D006623:von Hippel-Lindau Disease / Q000235:genetics* / Q000473:pathology / Q000601:surgery
chemical_list: D002274:Carcinogens, Environmental