Genome rearrangement in nonsmoking lung adenocarcinoma occurs as early as 30 years before cancer diagnosis
Last Update: 2020-06-19
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Image from cell, 2019, doi:10.1016/j.cell.2019.05.013 。< br / > these researchers confirmed that gene fusion in nonsmokers mostly occurs early, sometimes as early as childhood or adolescence, on average 30 years before the diagnosis of lung cancerThe study showed that the mutant lung cells carrying oncogenic seeds had been dormant for decades, and did not progress to lung cancer until many other mutations were fully accumulatedThis is the first study to reveal the structural variation landscape of lung adenocarcinoma genome< br / > lung cancer is the main cause of cancer-related death in the worldLung adenocarcinoma is the most common type of lung cancerMost lung adenocarcinoma is associated with long-term smoking, but about a quarter of lung adenocarcinoma is produced in nonsmokersTo be exact, it's still unclear what causes non-smokers to develop this cancer< br / > in this new study, the researchers used whole genome sequencing to analyze the genomes of 138 patients with lung adenocarcinoma, including smokers and non-smokersThey explored DNA damage that induces tumorigenic transformation< br / > lung adenocarcinoma derived from long-term smoking is called S4 high cancer in this study, which shows several significant features compared with lung adenocarcinoma unrelated to smoking (i.eS4 low cancer)The majority of patients in the group with high S4 cancer were older, male and mutated more frequently in the cancer-related gene KRASThe cancer genome in the S4 high cancer group had high frequency mutations in simple mutation types, such as substitution, insertion, or deletion of a single base< br / > but this situation is very different in the S4 low cancer groupIn general, the mutation spectrum of S4 low cancer group was more silent than that of S4 high cancer groupHowever, all cancer-related gene fusions - the abnormal activation of two initially separate genes by fusion - were only observed in the S4 low cancer group < br / > the pattern of genomic structural changes leading to gene fusion suggests that about three-quarters of gene fusion cases come from single cell crises in normal lung epithelium that lead to a large number of genomic fragmentation and subsequent imprecise repair < br / > most notably, these major genomic rearrangements leading to lung adenocarcinoma are likely to occur decades before the cancer is diagnosed The researchers used genomic archaeology to track the timing of these catastrophic events < br / > the researchers started the study seven years ago, when they first found the expression of the kif5b-ret fusion gene in lung adenocarcinoma < br / > Professor young Seok Ju of KAIST Graduate School of medical science and engineering, co-author of the paper, said, "it is worth noting that tumorigenesis can start with a large number of chromosome fragments in early life Our research immediately raised a new question: what induced this catastrophe in our normal lung epithelium? " < br / > Professor young Tae Kim of Seoul National University, co-author of the paper, said, "we hope that this study will help us to take a step forward in precision medicine for lung cancer patients." < br / > these researchers plan to further focus on the molecular mechanism of promoting complex rearrangement in vivo by screening the genome structure of fusion genes in other cancer types < br / > reference: Jake June Koo Lee et al.Tracing Oncogene Rearrangements in the Mutational History of Lung Adenocarcinoma Cell, 2019, doi:10.1016/j.cell.2019.05.013.
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