Cancer-Driving Mutations Common in Healthy Bladder Tissue According to Study

According to a study published in Science evaluating DNA changes in healthy and diseased human bladder tissue, ‘cancer-driving’ mutations are common in healthy bladder tissue.

The data found that a wide range of factors influence how bladder cancer develops as a result of examining individuals, which found that high variation in numbers and types of changes influence the development of bladder cancer.

"One of the questions we sought to answer with this study was why bladder cancers have some of the highest mutation rates and cancer-driving mutations of any cancer type, even though the cells in the bladder divide slowly, reducing the chance of a genetic error,” said first author of the study Andrew Lawson in a press release. “The high patient-to-patient variation in which genes were mutated and in the types of mutations may be consistent with the wide variety of factors that can contribute to bladder cancer. Further studies on the causes behind this variation could help uncover hidden causes of bladder cancer."

The researchers examined DNA sequencing to understand genetic changes in both healthy and diseased bladder tissue provided by clinicians at the University of Cambridge from 5 patients with bladder cancer and 15 patients with no history of cancer.

Following that examination, researchers took 2097 biopsies from the tissue sample and isolated the segments of a few hundred cells using laser-capture microscopy. More, the DNA from these samples was genome sequenced, then the sequences were analyzed to “characterize the landscape of somatic mutations.”

The examination revealed an unexpected high variability in the number of mutations, the types of mutations, and the frequency in ‘cancer-driving’ mutations. These findings suggest that a number of different factors impact the accumulation of mutations in the bladder. These factors could be distinguished by some of their mutational signatures in the genome.

"Like many cancers, early diagnosis of bladder cancer gives the patient a much greater chance of survival,” Thomas Mitchell, a senior author of the study, said in a press release. “The presence of mutations in key cancer genes in bladder tumours that are usually absent in normal tissue opens up the possibility of looking for these changes in fragments of DNA that are present in urine. These 'liquid biopsies' could be a non-invasive way to screen for bladder cancer earlier, which could help reduce the number of people who die from this disease."

A new mutational signature was identified by researchers that is associated with smoking, which provides context as to why tobacco is a great risk of developing bladder cancer. Specifically, the chemicals in tobacco products filter through the kidneys and contact the bladder on its way exiting the body.

Finding that mutations in key cancer genes were absent from healthy bladder tissue more often than not despite the high number of overall mutations surprised the authors. Since mutations in these genes are common in bladder cancer tumors, this means that their presence is a strong indicator that disease has set in.

"This study reveals an unexpectedly rich landscape of mutation and selection in normal bladder, with large differences across individuals driven to some extent by our daily exposures,” said lead author of the study, Dr. Inigo Martincorena, in a press release. “Thanks to technical advances, our understanding of how our cells mutate, compete and evolve as we age have been transformed over the last few years. In addition to shedding light on the origins of cancer and informing early detection efforts, these observations raise questions about the possible role of these widespread mutations in ageing and other diseases."

Reference:

DNA changes in healthy bladder provide clues on how cancer arises [news release]. Published October 1, 2020. https://www.eurekalert.org/pub_releases/2020-10/wtsi-dci093020.php. Accessed October 19, 2020.