Oncotarget

Priority Research Papers:

Age-related somatic mutations in the cancer genome

Brandon Milholland, Adam Auton, Yousin Suh, Jan Vijg _

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Oncotarget. 2015; 6:24627-24635. https://doi.org/10.18632/oncotarget.5685

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Abstract

Brandon Milholland1, Adam Auton1, Yousin Suh1 and Jan Vijg1

1 Albert Einstein College of Medicine, Bronx, NY, USA

Correspondence to:

Yousin Suh, email:

Jan Vijg, email:

Keywords: genomics, sequencing, aging, somatic mutation, bioinformatics

Received: September 04, 2015 Accepted: September 15, 2015 Published: September 17, 2015

Abstract

Aging is associated with an increased risk of cancer, possibly in part because of an age-related increase in mutations in normal tissues. Due to their extremely low abundance, somatic mutations in normal tissues frequently escape detection. Tumors, as clonal expansions of single cells, can provide information about the somatic mutations present in these cells prior to tumorigenesis.

Here, we used data from The Cancer Genome Atlas (TCGA), to systematically study the frequency and spectrum of somatic mutations in a total of 6,969 patients and 34 different tumor types as a function of the age of the patient. After using linear modeling to control for the age structure of different tumor types, we found that the number of identified somatic mutations increases exponentially with age. Using additional data from the literature, we found that accumulation of somatic mutations is associated with cell division rate, cancer risk and cigarette smoking, with the latter also associated with a distinct spectrum of mutations.

Our results confirm that aging is associated with the accumulation of somatic mutations, and strongly suggest that the level of genome instability of normal cells, modified by both endogenous and environmental factors, is the main risk factor for cancer.


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