Release date: 2017-11-08
Smoking and air pollution are two major public health problems facing the world, which can cause mutations in the human genome and cause diseases. There are 1.82 million new cases of lung cancer every year worldwide, and 1.59 million people die of lung cancer. 85% of lung cancer is caused by smoking, and air pollution causes 220,000 new cases of lung cancer every year. In order to reveal the mechanism of lung cancer, researchers often use the normal lung tissue adjacent to the cancer as a control to analyze the abnormalities of lung cancer genome. However, normal lung tissue adjacent to the cancer is also exposed to smoking and air pollution, and whether genomic mutations have also occurred has not been noticed so far.
The Zhou Guangyu Research Group of the Institute of Zoology, Chinese Academy of Sciences used the "normal control-cancer tissue" pairing method to perform genome-wide sequencing of 11 cases of lung adenocarcinoma patients and 3 cases of adjacent normal lung tissues and corresponding cancer tissues of patients with lung squamous cell carcinoma. The data were compared with normal human genomic sequences, single nucleotide polymorphism databases, and errors due to poor sequencing quality were excluded, and mutations found only in normal lung tissue but not in cancer tissues were found. Using polymerase chain reaction product sequencing, the researchers verified these mutations that occurred only in normal control lung tissue (see figure) and referred to them as pairer normal control (CNC) genomic variation. They further analyzed the results of sequencing the entire exome of 513 lung adenocarcinomas and 478 patients with lung squamous cell carcinoma in the US Cancer Genome Atlas (TCGA) database, and found mutations in only normal control tissues.
In lung adenocarcinoma patients, there are 0.27 mutations per 1 million bases in the exon of normal control tissues, and 5.3 gene mutations in each specimen; the average exon of normal control tissue of lung squamous cell carcinoma patients per million bases There are 0.57 mutations in the base, and each sample contains 7.8 gene mutations. In the normal control tissues of patients with lung adenocarcinoma and squamous cell carcinoma, C:G→T:A has the highest base substitution ratio, which is the genomic scar caused by the tobacco carcinogen methylnitronitroguanidine (MNNG). One perspective illustrates the important role of environmental factors in the development of lung cancer. Mutations in some genes are associated with poor patient prognosis, while other gene mutations are associated with better patient outcomes. This indicates that there are also genomic mutations in normal tissues adjacent to the smoker's cancer. When the mutation continues to accumulate, new tumor lesions may form, so lung cancer is likely to be of polyclonal origin.
Relevant research results were published in Oncotarget and Frontiers of Medicine, the Chinese Academy of Engineering. The project was supported by the National Natural Science Foundation Outstanding Youth Science Fund, the National Key Research and Development Program for Precision Medicine Research, and the Strategic Pilot Program of the “Individualized Drugs – Pragmatic New Drug Development Based on Disease Molecular Classification†by the Chinese Academy of Sciences.
Source: Animal Research Institute
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