This article is original to the Translational Medicine Network. Please indicate the source when reprinting. Author: Mia Introduction: Somatic mutations refer to mutations that occur in somatic cells other than sex cells. It will not cause genetic changes in future generations, bu

This article is original to the Translational Medicine Network. Please indicate the source when reprinting.

Author: Mia

Introduction: Somatic cell mutation refers to mutations that occur in somatic cells except sex cells. It will not cause genetic changes in future generations, but it can cause changes in the genetic structure of certain cells in the present generation. Recently, a study performed gene-based rare variant association studies using human cancer genomes from more than 11,000 individuals of European ancestry and discovered distinct mutational processes.

somatic mutations are an inevitable part of aging and the most important cause of cancer. Somatic mutations are mutations that occur in somatic cells other than sex cells and therefore usually do not cause genetic changes in offspring. Somatic mutations, caused by a host of factors such as age and smoking, are a major cause of cancer and also have an impact on other diseases.

Research led by ICREA researchers Dr. Fran Supek at the Institute of Biomedical Research in Barcelona (IRB Barcelona) and Dr. Ben Lehner at the Center for Genomic Regulation (CRG) identified genetic traits in individuals that are prone to specific somatic mutations in their tissues. People with higher mutation rates in their organs are more likely to accumulate mutations in key cancer genes, which increases the risk of tumor formation. The paper of this research was published in "Nature Communications" .

https://www.nature.com/articles/s41467-022-31483-1#citeas

Although many tumors have no clear genetic explanation, researchers have previously described genetic mechanisms that make individuals more susceptible to cancer. Conceivably, cancer risk may result from changes in different types of somatic mutational repertoires, a common cause of cancer.

Dr. Mischan Vali Pour, who led the study in the labs of Drs. Lehner and Supek, said: "In this comprehensive study, we examined whether the different types of DNA changes observed in tumors by were related to many genes. Genetic variants of and are related to . We developed a new method that identified 42 genes associated with 15 different cellular mechanisms that influence the risk of different somatic mutations that will help explain cancer susceptibility. "While several genes that alter somatic mutation patterns have previously been identified, such as the BRCA gene that predisposes to breast cancer and ovarian cancer," said Dr. Fran Supek, head of the Genomic Data Science Laboratory at IRB Barcelona. and Lynch syndrome genes that predispose to colon cancer . But we have now identified many other genes that can similarly influence somatic mutation accumulation.

Future work based on this study may help assess a patient's genetic risk for developing specific cancers. , we are therefore able to personalize prevention programs or detect relevant diseases at an early stage . In addition, we will also be able to personalize cancer treatments for patients by detecting somatic mutation signatures, as another study by Barcelona IRB showed.

Genomic Instability and Cancer Risk

01 Most of the mechanisms arising from

mutations are related to defects in the repair of damaged DNA. This results in a phenomenon of genomic instability that reduces the time required for the emergence of two to 10 tumorigenic mutations in cancer driver genes.

At the same time, each of the identified mechanisms brings about different types of mutations, or mutations in different regions of the genome, and therefore, can be linked to the emergence of cancers in specific organs.

Statistical and machine learning methods

02

To make these predictions, the researchers developed an approach based on statistical genomics and machine learning models - "autoencoders" neural networks - that can find patterns in complex data.

But this study has a limitation: The genetic factors associated with somatic mutations are highly variable, and each of these factors has a relatively low incidence rate. Study The number of available genome sequences limits the ability to discover links between genes and mutations. If more genomic data can be collected from cancer patients of non-European ancestry, researchers may be able to make further discoveries.

Lehner concluded: "As more genetic data become available, we have the opportunity to discover more genetic susceptibility factors that contribute to cancer mutations. The 'rare' genetic variants we considered in this study, although they only exist in a small number of individuals, but collectively are critical in shaping the cancer genome and underlying cancer risk ”

Reference:

https://medicalxpress.com/news/2022-07-hereditary-factors-likelihood-cancer-mutations. .html

Note: This article is intended to introduce the progress of medical research and cannot be used as a reference for treatment plans. If you need health guidance, please go to a regular hospital.

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