Báo cáo khoa học
- De novo Variants of Dominant Monogenic Disorders in Vietnam Detected by a Noninvasive Prenatal Test: A Case Series
Noninvasive prenatal tests for monogenic diseases (NIPT-SGG) have recently been reported as helpful in early-stage antenatal screening. Our study describes the clinical and genetic features of cases identified by NIPT-SGG. Materials&methods: In a cohort pregnancy with abnormal sonograms, affected cases were confirmed by invasive diagnostic tests concurrently, with NIPT-SGG targeting 25 common dominant single-gene diseases.
- Establishment and Assessment of a Non-invasive Prenatal Testing Protocol for 22q11.2 Deletion Syndrome
We established a non-invasive prenatal testing protocol to screen for fetal microdeletion, specifically at 22q11.2 causing DiGeorge syndrome. This is an important step towards expanding the scope of current noninvasive prenatal testing to detect a wide spectrum of fetal diseases caused by microdeletion
- Combined Gap-Polymerase Chain Reaction and Targeted Next-Generation Sequencing Improve α- and β-Thalassemia Carrier Screening in Pregnant Women in Vietnam
Vietnam has a high thalassemia burden. We collected blood samples from 5880 pregnant Vietnamese women during prenatal health checks to assess thalassemia carrier frequency using combined gap-polymerase chain reaction (gap-PCR) and targeted next-generation sequencing (NGS).
- Detection of maternal carriers of common α-thalassemia deletions from cell-free DNA
α-Thalassemia is a common inherited blood disorder manifested mainly by the deletions of α-globin genes. In geographical areas with high carrier frequencies, screening of α-thalassemia carrier state is therefore of vital importance.
- Genetic profiling of Vietnamese population from large-scale genomic analysis of non-invasive prenatal testing data
The under-representation of several ethnic groups in existing genetic databases and studies have undermined our understanding of the genetic variations and associated traits or diseases in many populations.
- High prevalence of maternal mosaic monosomy X in pregnant women in Vietnam
To demonstrate the prevalence of maternal mosaic monosomy X (MMXO) in a cohort of pregnant women in Vietnam.
- Genetic profiling of 2,683 Vietnamese genomes from non-invasive prenatal testing data.
The under-representation of Vietnamese ethnic groups in existing genetic databases and studies have undermined our understanding of the genetic variations and associated traits or diseases in the population.
- Reducing false positive rate of fetal monosomy X in non-invasive prenatal testing using a combined algorithm to detect maternal mosaic monosomy X.
The false positive rate of detecting monosomy X by NIPT is higher than that of other autosomal aneuploidies, due in part to maternal mosaic monosomy X.
- Establishing and validating noninvasive prenatal testing procedure for fetal aneuploidies in Vietnam.
Noninvasive prenatal testing (NIPT) for fetal aneuploidies has been widely adopted in developed countries. Despite the sharp decrease in the cost of massively parallel sequencing, the technical know-how and skilled personnel are still one of the major limiting factors for applying this technology to NIPT in low-income settings.
- Genetic landscape of recessive diseases in the Vietnamese population from large-scale clinical exome sequencing
Accurate profiling of population-specific recessive diseases is essential for the design of cost-effective carrier screening programs. However, minority populations and ethnic groups, including Vietnamese, are still underrepresented in existing genetic studies.
- Combination of Hotspot Mutations With Methylation and Fragmentomic Profiles to Enhance Multi-Cancer Early Detection
- Breast cancer risk assessment based on susceptibility genes and polygenic risk score in Vietnamese women
This study provides the first large datasets for HBOC gene analysis, BC susceptibility SNP association testing, and PRS modeling for Vietnamese women. Together, these data could aid the development of personalized BC screening recommendations for women in Vietnam.
- Evaluation of a multimodal ctDNA-based assay for detection of aggressive cancers lacking standard screening tests
- Clinical trial and real-world evidence of circulating tumor DNA monitoring to predict recurrence in patients with resected colorectal cancer
Circulating tumor DNA (ctDNA) is a novel biomarker for predicting recurrence in colorectal cancer (CRC). Analysis from both clinical trials and real-world data indicates that ctDNA serves as an independent and strong prognostic biomarker for CRC recurrence. ctDNA testing may aid clinical decision-making by supporting personalized intervention and surveillance strategies.
- A consultation and work-up diagnosis protocol for a multicancer early detection test: a case series study
The emergence of multicancer early detection (MCED) tests holds promise for improving early cancer detection and public health outcomes. However, positive MCED test results require confirmation through recommended cancer diagnostic imaging modalities. To address these challenges, we have developed a consultation and work-up protocol for definitive diagnostic results post MCED testing, named SPOT-MAS. Developed through circulating tumor DNA (ctDNA) analysis and in line with professional guidelines and advisory board consensus, this protocol standardizes information to aid general practitioners in accessing, interpreting and managing SPOT-MAS results. Clinical effectiveness is demonstrated through a series of identified cancer cases. Our research indicates that the protocol could empower healthcare professionals to confidently interpret circulating tumor DNA test results for 5 common types of cancer, thereby facilitating the clinical integration of MCED tests.
- Circulating DNA methylation profile improves the accuracy of serum biomarkers for the detection of nonmetastatic hepatocellular carcinoma
This study exploited hepatocellular carcinoma (HCC)-specific circulating DNA methylation profiles to improve the accuracy of a current screening assay for HCC patients in high-risk populations.
- Ultra-Deep Massive Parallel Sequencing of Plasma Cell-Free DNA Enables Large-Scale Profiling of Driver Mutations in Vietnamese Patients With Advanced Non-Small Cell Lung Cancer
Population-specific profiling of mutations in cancer genes is of critical importance for the understanding of cancer biology in general as well as the establishment of optimal diagnostics and treatment guidelines for that particular population.
- Tissue of origin detection for cancer tumor using low-depth cfDNA samples through combination of tumor-specific methylation atlas and genome-wide methylation density in graph convolutional neural networks
We have demonstrated that our TSMA in combination with other cfDNA features can improve TOO detection in low-depth cfDNA samples.
- Analytical validation and clinical utilization of K-4CARE™: a comprehensive genomic profiling assay with personalized MRD detection
K-4CARE™ assay provides comprehensive and reliable genomic information that fulfills all guideline-based biomarker testing for both targeted therapy and immunotherapy. Integration of ctDNA tracking helps clinicians to further monitor treatment response and ultimately provide well-rounded care to cancer patients.
- Multimodal analysis of methylomics and fragmentomics in plasma cell-free DNA for multi-cancer early detection and localization
eLife assessment: This study provides insights into the early detection of malignancies with noninvasive methods by developing a framework, which assesses methylation, CNA, and other genomic features. They established a solid model in discriminating malignancies from healthy controls, as well as the ability to distinguish tumor of origin. This important study will demonstrate its practical impacts in the clinic and other researchers of the field.
- Prevalence and genetic spectrum associated with hereditary colorectal cancer syndromes, the need to improve cancer risk awareness, and family cascade testing in Vietnam
Of all genetic test results, 3% (49/1632) were identified with mutations related to HCCS. Over 77% of them belonged to Lynch syndrome. PMS2 appeared to be the gene with the highest mutation frequency, while MLH1 was the lowest. This study provided new evidence for HCCS mutation spectrum in Vietnamese population and the success in promoting cascade test in high-risk family members through financial and technical support.
- Multimodal analysis of genome-wide methylation, copy number aberrations, and end motif signatures enhances detection of early-stage breast cancer
The article showed that a multimodal liquid biopsy assay based on analysis of cfDNA methylation, CNA and EM could enhance the accuracy for the detection of early- stage breast cancer. By identifying distinct profiles of genome-wide methylation changes (GWM), copy number alterations (CNA), and 4-nucleotide oligomer (4-mer) end motifs (EM) in cfDNA of breast cancer patients, combination model outperformed base models built from individual features, achieving an AUC of 0.91 (95% CI: 0.87-0.95), a sensitivity of 65% at 96% specificity.
- Fragment length profiles of cancer mutations enhance detection of circulating tumor DNA in patients with early-stage hepatocellular carcinoma
Our model achieved an area under the curve (AUC) of 0.88, a sensitivity of 89%, and a specificity of 82% in the discovery cohort consisting of 55 PwHCC and 55 healthy participants. In an independent validation cohort of 54 PwHCC and 53 healthy participants, the established model achieved comparable classification performance with an AUC of 0.86 and yielded a sensitivity and specificity of 81%.
- Clinical validation of a ctDNA-Based Assay for Multi-Cancer Detection: An Interim Report from a Vietnamese Longitudinal Prospective Cohort Study of 2795 Participants
Our analysis of 2795 participants from 14 sites across Vietnam demonstrates its ability to detect cancers in asymptomatic individuals with a positive predictive value of 60%, with 83.3% accuracy in detecting tumor location.
- Pathogenic Variant Profile of Hereditary Cancer Syndromes in a Vietnamese Cohort
Hereditary cancer syndromes (HCS) are responsible for 5-10% of cancer cases. Genetic testing to identify pathogenic variants associated with cancer predisposition has not been routinely available in Vietnam. Consequently, the prevalence and genetic landscape of HCS remain unknown.
- Building the procedure of SPOT-MAS technology: multiple cancer early detection
Evaluate SPOT-MAS performance on detection of 4 common cancer types AUC 0.93; SEN: 73.9%; SPEC 95.9%
- Liquid biopsy uncovers distinct patterns of DNA methylation and copy number changes in NSCLC patients with different EGFR-TKI resistant mutations
Targeted therapy with tyrosine kinase inhibitors (TKI) provides survival benefits to a majority of patients with non-small cell lung cancer (NSCLC). However, resistance to TKI almost always develops after treatment.
- Evaluation of a Liquid Biopsy Protocol using Ultra-Deep Massive Parallel Sequencing for Detecting and Quantifying Circulation Tumor DNA in Colorectal Cancer Patients
The identification and quantification of actionable mutations are critical for guiding targeted therapy and monitoring drug response in colorectal cancer. Liquid biopsy (LB) based on plasma cell-free DNA analysis has emerged as a noninvasive approach with many clinical advantages over conventional tissue sampling.
- Tumor genomic profiling and personalized tracking of circulating tumor DNA in Vietnamese colorectal cancer patients
Colorectal cancer (CRC) is the fifth most common cancer with rising prevalence in Vietnam. However, there is no data about the mutational landscape and actionable alterations in the Vietnamese patients.
- Genetic landscape and personalized tracking of tumor mutations in Vietnamese women with breast cancer.
Using top-ranked mutations, we detected ctDNA in pre-operative plasma in 24.6–43.5% of the hormone-receptor-positive groups and 76.9–80.8% of the hormone-receptor-negative groups. The detection rate was associated with breast cancer subtypes and clinicopathological features that increased the risk of relapse. Interim analysis after a 15-month follow-up revealed post-operative detection of ctDNA in all three patients that had recurrence, with a lead time of 7–13 months ahead of clinical diagnosis.
- Multimodal analysis of ctDNA methylation and fragmentomic profiles enhances detection of nonmetastatic colorectal cancer.
Early detection of colorectal cancer (CRC) provides substantially better survival rates. This study aimed to develop a blood-based screening assay named SPOT-MAS (‘screen for the presence of tumor by DNA methylation and size’) for early CRC detection with high accuracy.
- Ultra-Deep Sequencing of Plasma-Circulating DNA for the Detection of Tumor- Derived Mutations in Patients with Nonmetastatic Colorectal Cancer
Identification of tumor-derived mutation (TDM) in liquid biopsies (LB), especially in early-stage patients, faces several challenges, including low variant-allele frequencies, interference by white blood cell (WBC)-derived mutations (WDM), benign somatic mutations and tumor heterogeneity.
- Ultra-Deep Massive Parallel Sequencing of Plasma Cell-Free DNA Enables Large-Scale Profiling of Driver Mutations in Vietnamese Patients With Advanced Non-Small Cell Lung Cancer
Population-specific profiling of mutations in cancer genes is of critical importance for the understanding of cancer biology in general as well as the establishment of optimal diagnostics and treatment guidelines for that particular population.
- Actionable Mutation Profiles of Non-Small Cell Lung Cancer patients from Vietnamese population | Scientific Reports
Comprehensive profiling of actionable mutations in non-small cell lung cancer (NSCLC) is vital to guide targeted therapy, thereby improving the survival rate of patients.
- Ultra-deep massively parallel sequencing with unique molecular identifier tagging achieves comparable performance to droplet digital PCR for detection and quantification of circulating tumor DNA from lung cancer patients
The identification and quantification of actionable mutations are of critical importance for effective genotype-directed therapies, prognosis and drug response monitoring in patients with non-small-cell lung cancer (NSCLC).
- Clinical and genetic features of congenital bile acid synthesis defect with a novel mutation in AKR1D1 gene sequencing
- Massively parallel sequencing uncovered disease-associated variant spectra of glucose-6-phosphate dehydrogenase deficiency, phenylketonuria and galactosemia in Vietnamese pregnant women
- Genetic analysis of Vietnamese patients with early-onset Alzheimer’s disease
- Novel compound heterozygous TMEM67 variants in a Vietnamese family with Joubert syndrome: a case report
- Detection of a heterozygous germline APC mutation in a three-generation family with familial adenomatous polyposis using targeted massive parallel sequencing in Vietnam
- KO of 5-InsP7 kinase activity transforms the HCT116 colon cancer cell line into a hypermetabolic, growth-inhibited phenotype
- The Significance of the Bifunctional Kinase/Phosphatase Activities of Diphosphoinositol Pentakisphosphate Kinases (PPIP5Ks) for Coupling Inositol Pyrophosphate Cell Signaling to Cellular Phosphate Homeostasis
- The Galpha4 G protein subunit interacts with the MAP kinase ERK2 using a D-motif that regulates developmental morphogenesis in Dictyostelium
- Opening the conformation is a master switch for the dual localization and phosphatase activity of PTEN
- Engineering PTEN function: membrane association and activity
- Identification of a functional nuclear translocation sequence in hPPIP5K2.
- Engineering ePTEN, an enhanced PTEN with increased tumor suppressor activities
- MAP kinases have different functions in Dictyostelium G protein-mediated signaling
- MAPKs in development: insights from Dictyostelium signaling pathways.
- G{alpha}5 subunit-mediated signaling requires a D-motif and the MAPK ERK1 in Dictyostelium
- Loss of cAMP-specific phosphodiesterase rescues spore development in G protein mutant in dictyostelium
