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

Suzanne S. Fei, Asia D. Mitchell, Michael B. Heskett, Cathy D. Vocke, Christopher J. Ricketts, Myron Peto, Nicholas J. Wang, Mustafa (Kemal) Sonmez, W. Marston Linehan, Paul Spellman

Research output: Contribution to journalArticle

12 Citations (Scopus)

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.

Original languageEnglish (US)
Article number11588
JournalNature Communications
Volume7
DOIs
StatePublished - May 13 2016

Fingerprint

von Hippel-Lindau Disease
Tumors
tumors
Kidney
Neoplasms
Nucleotides
nucleotides
mutations
Chromosomes
cancer
Aberrations
Random processes
Stochastic Processes
Mutation
Animals
Substitution reactions
sequencing
genome
Genes
chromosomes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Physics and Astronomy(all)

Cite this

Patient-specific factors influence somatic variation patterns in von Hippel-Lindau disease renal tumours. / Fei, Suzanne S.; Mitchell, Asia D.; Heskett, Michael B.; Vocke, Cathy D.; Ricketts, Christopher J.; Peto, Myron; Wang, Nicholas J.; Sonmez, Mustafa (Kemal); Linehan, W. Marston; Spellman, Paul.

In: Nature Communications, Vol. 7, 11588, 13.05.2016.

Research output: Contribution to journalArticle

Fei, SS, Mitchell, AD, Heskett, MB, Vocke, CD, Ricketts, CJ, Peto, M, Wang, NJ, Sonmez, MK, Linehan, WM & Spellman, P 2016, 'Patient-specific factors influence somatic variation patterns in von Hippel-Lindau disease renal tumours', Nature Communications, vol. 7, 11588. https://doi.org/10.1038/ncomms11588
Fei, Suzanne S. ; Mitchell, Asia D. ; Heskett, Michael B. ; Vocke, Cathy D. ; Ricketts, Christopher J. ; Peto, Myron ; Wang, Nicholas J. ; Sonmez, Mustafa (Kemal) ; Linehan, W. Marston ; Spellman, Paul. / Patient-specific factors influence somatic variation patterns in von Hippel-Lindau disease renal tumours. In: Nature Communications. 2016 ; Vol. 7.
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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.",
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AU - Wang, Nicholas J.

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