DNA突变,膀胱癌 z-bo 2020-10-23 358

　　In a recent study, the first comprehensive study of DNA mutations in bladder tissue in healthy and bladder cancer patients showed that "cancer-driven" mutations are common in healthy bladder tissue. This research, conducted by scientists at the Wellcome Sanger Institute at Cambridge University and their collaborators, provides an unprecedented perspective on the first step of bladder cancer.

　　The study was published today in the journal Science and found that there are high differences in the number and types of changes between individuals, indicating that there are many factors that affect the development of bladder cancer. The researchers also provided new insights into the link between smoking and bladder cancer.

　　In the UK, more than 10,000 people are diagnosed with bladder cancer each year, and about 5,000 of them die. Approximately 60% of new cases occur in people over 75 years of age. It is estimated that about half of bladder cancer cases are preventable. Early diagnosis is also crucial. Among them, 95% of early diagnoses survived for a year or more, while the number of late diagnoses dropped to 36%.

　　Cancer is caused by changes in DNA (called somatic mutations), and this change occurs continuously throughout our life cycle. Some somatic mutations, especially those that affect known "cancer genes", confer a competitive advantage, allowing these mutant cells to expand faster than normal cells and may lead to cancer.

　　The development of

　　technology enables people to detect somatic mutations related to cancer in normal tissues, thereby obtaining relevant information about cancer at an early stage, and increasing the chance of early detection and treatment.

　　This new study uses DNA sequencing technology to better understand the genetic changes in healthy and diseased bladder tissue. Clinicians at the University of Cambridge donated bladder tissue from five people with bladder cancer and 15 people without a history of cancer.

　　Then, researchers at the Wellcome Sanger Institute used a technique called laser capture microscopy to extract 2,097 biopsy samples from tissue samples to separate fragments of only a few hundred cells. Genomic sequencing of the DNA from these samples and sequence analysis to characterize somatic mutations.

　　The research team found that the number and type of mutations and the unexpectedly high variability in the frequency of mutations that "drive cancer" among individuals indicate that a wide range of factors affect the accumulation of mutations in the bladder. Some of these factors can be identified by their "mutation characteristics"-a typical pattern of genomic mutations caused by a certain chemical or process.

　　The study identified new mutation characteristics associated with smoking, thereby clarifying why tobacco is the biggest risk associated with bladder cancer. Although the bladder is not in direct contact with smoke, the chemicals in tobacco products are filtered out by the kidneys and come into contact with the bladder in urine.

　　In addition, the researchers found that, despite the high number of mutations in total, there are basically no mutations in key cancer genes such as TP53, FGFR3, and TERT in healthy bladder tissue. Because mutations in these genes are common in bladder tumors, their presence is a powerful indicator of the beginning of the disease.