The National Institutes of Health (NIH), a part of the US Department of Health and Human Services, has uncovered the mystery of how lung cancer develops in people who have never smoked and more precisely clinical treatments. can guide the development of Genomic analysis of lung cancers in people with a history of smoking has found that most of these tumors result from the accumulation of mutations caused by natural processes in the body.
The study was conducted by an international team led by researchers from the National Cancer Institute (NCI), part of the National Institutes of Health (NIH) and describes three molecular subtypes of lung cancer in non-smokers for the first time. The findings were published earlier this week in Nature Genetics.
“What we are seeing is that non-smokers have different subtypes of lung cancer that have distinct molecular features and evolutionary processes,” says epidemiologist Maria, MD, PhD, of the Integrative Tumor Epidemiology Branch in the NCI’s Division. Teresa Landi said. of cancer epidemiology and genetics, who led the study, which was carried out in collaboration with researchers from the National Institute of Environmental Health Sciences, another part of the NIH, and other institutions. “In the future we may be able to do different treatments based on these subtypes.”
Lung cancer is the leading cause of cancer-related death worldwide. Every year, more than 2 million people worldwide are diagnosed with this disease. Environmental risk factors, such as exposure to radon, air pollution and asbestos, or having previous lung diseases, may explain some lung cancers in non-smokers, but scientists still do not know which of these What is the cause of most cancers?
In this large epidemiological study, researchers used whole-genome sequencing to characterize genomic changes in tumor tissue and matched normal tissue from 232 smokers, mainly of European descent, who were considered non-smokers. Was diagnosed with small cell lung cancer. Tumors included 189 adenocarcinomas (the most common type of lung cancer), 36 carcinoids, and seven other tumors of various types. The patients had not yet received treatment for their cancer.
The researchers combed the tumor genome for mutational signatures, which are patterns of mutations associated with specific mutational processes, such as damage from natural activities in the body (for example, defective DNA repair or oxidative stress) or from exposure to carcinogens. Mutational signatures act like a collection of tumor activities that lead to the accumulation of mutations, providing clues as to the cause of cancer development. A list of known mutual signatures now exists, although some signatures have no known cause. In this study, researchers found that most tumor genomes in non-smokers contain mutational signatures associated with damage from endogenous processes, that is, natural processes within the body.
As expected, because the study was limited to non-smokers, the researchers did not find any mutational signatures associated with direct exposure to prior tobacco smoking.
Genomic analysis also revealed three novel subtypes of lung cancer in never-smokers, for which the researchers named music based on the level of “noise” (i.e. the number of genomic changes) in the tumor. The dominant “piano” subtype had the fewest mutations; It appears to be associated with the activation of progenitor cells, which are involved in the formation of new cells.
This subtype of tumor grows very slowly over many years, and is difficult to treat because it can contain many different driver mutations. The “Mezo-Forte” subtype had specific chromosomal alterations as well as mutations in the growth factor receptor gene EGFR, which is commonly altered in lung cancer, and displayed rapid tumor growth. The “fort” subtype exhibited whole-genome doubling, a genomic one. Changes often seen in lung cancer in smokers. This subtype of tumor also grows rapidly.
“We are starting to differentiate those subtypes which could potentially lead to different approaches to prevention and treatment,” said Dr. Landi. For example, the slow-growing Piano subtype may allow clinicians to detect these tumors when they first are less difficult to treat. In contrast, the Mezzo-Forte and Forte subtypes contain only a few key driver mutations. , suggesting that these tumors can be identified by a biopsy and may benefit from targeted treatment, she said.
A future direction of this research will be to study people from different ethnic backgrounds and geographic locations, and whose exposure history to risk factors for lung cancer is well described.
“We are just at the beginning of understanding how these tumors develop,” said Dr. Landi. This analysis suggests that there is no diversity or diversity in lung cancer among smokers. “
The director of the NCI’s Department of Cancer Epidemiology and Genetics, Stephen J. “We expect that this detective-style investigation of genomic tumor characteristics will open new avenues of discovery for many types of cancer,” Channock said.
The study was conducted by the Intramural Research Program of the NCI and the National Institute of Environmental Health Sciences.
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