Magen helps the success of Cell-free DNA Research and
Application

Tumor Diagnosis (Liquid Biopsy):

The cfDNA released by circulating tumor cells in plasma or in situ tumor cells into circulation in tumor patients is also called ctDNA. The research directions of ctDNA in tumor diagnosis mainly include: detection of ctDNA mutation, tumor specific microsatellite changes, epigenetic changes, ctDNA integrity detection and virus DNA detection. CtDNA mutation detection can not only obtain the gene mutation results corresponding to tumor tissues, but also more sensitively and specifically detect typical characteristic mutations such as EGFR gene mutation of lung cancer, KRAS mutation of colorectal cancer and BRAF mutation of melanoma.

Studies have shown that the sensitivity of EGFR gene mutation in ctDNA of lung cancer patients can be as high as 80%, which is conducive to monitoring drug resistance genes. The sensitivity and specificity of KRAS gene mutation in plasma ctDNA of patients with metastatic colorectal cancer were as high as 87.2% and 99.2%.

The integrity detection of tumor ctDNA is also the focus of current research. The main principle of integrity detection is that long and complete DNA fragments will be released during tumor necrosis, while cfDNA released by normal apoptotic cells is shorter. Detection of the integrity of ctDNA can be used to predict the development and micrometastasis of early cancer. In addition, studying the loss of gene heterozygosity in ctDNA and the methylation level of ctDNA can also provide help for tumor specific diagnosis and disease risk prediction. The methylation detection of ctDNA is also helpful to the early diagnosis of tumor.

Noninvasive prenatal testing:

CfDNA detection is also widely used in noninvasive prenatal testing (NIPT). The method for detecting cfDNA by NIPT is mainly developed based on next-generation sequencing technology (NGS), including random high-throughput parallel sequencing, target or chromosome specific sequencing and single nucleotide polymorphism sequencing. Fetal cfDNA in maternal plasma accounts for more than 10% of the total cfDNA in maternal plasma. Detecting these fetal cfDNA can determine the fetal RhD blood group, gender, chromosomal aneuploidy disease, single gene genetic disease and other related information. In addition, this method of detecting maternal plasma fetal cfDNA is less traumatic than invasive methods such as amniocentesis or villus biopsy, which greatly reduces the risk of complications such as intrauterine infection and abortion.

At present, it is mainly used to screen and judge common aneuploid chromosome diseases, including trisomy 21 syndrome, trisomy 18 syndrome and trisomy 13 syndrome. In addition, it has also been reported in sex chromosome aneuploidy diseases, chromosome microdeletions, copy number abnormalities and some single gene genetic diseases. Studies found that noninvasive prenatal screening cfDNA has high sensitivity (greater than 99%) and specificity, while the false positive rate is relatively low (less than 0.1%).

The international society for prenatal diagnosis (ISPD), the American College of Obstetricians and Gynaecologists (ACOG) and the American College of medicalgenetics and genomics (ACMG) all recommend pregnant women to carry out NIPT testing which helps the early diagnosis of chromosomal aneuploidy diseases (such as trisomy 21 syndrome) and monogenic genetic diseases during pregnancy.

Cardiovascular disease testing:

CfDNA mainly comes from apoptotic or necrotic cells. In this case, the content levelin plasma will increase due to the release of cfDNA into the blood. Coronary heart disease often leads to cardiomyocyte necrosis and apoptosis caused by long-term severe myocardial ischemia. Especially when myocardial infarction (MI) occurs, in addition to the increase of cfDNA caused by cardiomyocyte necrosis and apoptosis caused by myocardial ischemia, the delay and obstacle of cfDNA clearance are also related to the pathogenesis of the disease. The increase of plasma cfDNA in patients with coronary heart disease can be used to supplement the diagnostic results of cardiac troponin I (cTnI) and creatinekinase MB (CK-MB). Studies have shown that the plasma cfDNA concentration inpatients with MI is more than 10 times higher than that in healthy controls.