Identifying the Pathogenic Variants in Heart Genes in Vietnamese Sudden Unexplained Death Victims by Next-Generation Sequencing.

In forensics, one-third of sudden deaths remain unexplained after a forensic autopsy. A majority of these sudden unexplained deaths (SUDs) are considered to be caused by inherited cardiovascular diseases. In this study, we investigated 40 young SUD cases (<40 years), with non-diagnostic structural cardiac abnormalities, using Targeted NGS (next-generation sequencing) for 167 genes previously associated with inherited cardiomyopathies and channelopathies. Fifteen cases identified 17 variants on related genes including the following: AKAP9, CSRP3, GSN, HTRA1, KCNA5, LAMA4, MYBPC3, MYH6, MYLK, RYR2, SCN5A, SCN10A, SLC4A3, TNNI3, TNNI3K, and TNNT2. Of these, eight variants were novel, and nine variants were reported in the ClinVar database. Five were determined to be pathogenic and four were not evaluated. The novel and unevaluated variants were predicted by using in silico tools, which revealed that four novel variants (c.5187_5188dup, p.Arg1730llefsTer4 in the AKAP9 gene; c.1454A>T, p.Lys485Met in the MYH6 gene; c.2535+1G>A in the SLC4A3 gene; and c.10498G>T, p.Asp3500Tyr in the RYR2 gene) were pathogenic and three variants (c.292C>G, p.Arg98Gly in the TNNI3 gene; c.683C>A, p.Pro228His in the KCN5A gene; and c.2275G>A, p.Glu759Lys in the MYBPC3 gene) still need to be further verified experimentally. The results of our study contributed to the general understanding of the causes of SUDs. They provided a scientific basis for screening the risk of sudden death in family members of victims. They also suggested that the Targeted NGS method may be used to identify the pathogenic variants in SUD victims.

Multiple primary squamous cell carcinomas of the oral cavity: A cross-sectional study in vietnam.

Background: Multiple primary squamous cell carcinomas (MPSCs) of the oral cavity are very uncommon in clinical practice. This study describes the clinical features, imaging, and treatment characteristics of the oral cavity with MPSCs at the same time of diagnosis in our center. Besides, we review the literature and prior studies on MPSCs. Study design: A retrospective, descriptive study from January 2019 to December 2021 was conducted on seven patients with MPSCs of the oral cavity at the time of their first diagnosis. Evaluation of the patient's characteristics, the treatment plan, the response to treatment, and the overall survival (OS). Results: Seven male patients ranging in age from 43 to 70 years (Mean: 53.5). Positron Emission Tomography/Computed Tomography (PET/CT) revealed a significantly increased standardized uptake value (SUV) in the index tumor (SUVi = 15.76 ± 1.96). The index tumor is often staged T3, T4; whereas the synchronous tumor is typically staged T1, T2. All patients had concurrent chemoradiotherapy (CCRT) and achieved a partial response in all cases. Mean OS was 14.71 ± 11.85 months. Conclusions: MPSCs of the oral cavity at the time of diagnosis are uncommon and associated with a poor prognosis for patients. Comprehensive clinical examination, combined imaging diagnostics, with PET/CT being critical for detecting the second lesion, particularly in patients with an advanced index tumor.

SHOX2 methylation in Vietnamese patients with lung cancer.

BACKGROUND: DNA methylation on cytosine in the CpG dinucleotides is one of the most common epigenetic perturbations taking place during cancer initiation, progression, occurrence and resistance therapy. DNA methylation seems to be sufficiently stable epigenetic modification to be utilized as a cancer biomarker in in vitro diagnostic (IVD) settings. Nowadays, the SHOX2 methylation (mSHOX2) is one of the most valuable DNA methylation biomarkers of lung cancer that is the leading cause of cancer death. It is being continuously validated across ethnicities, lifestyles and lifespan. This study focused on characteristics of mSHOX2 in Vietnamese patients with lung cancer since a lack of investigation and evidence of its utility in this country. METHODS: The probe and primer sets were designed according to the MethyLight method for quantitative assessment of the mSHOX2 in 214 formalin-fixed paraffin-embedded (FFPE) lung tissues and 57 plasma samples. RESULTS: mSHOX2 in FFPE tissues allowed discriminating benign and malignant lung diseases with 60% (95% CI 50.7-68.8%) sensitivity and 90.4% (95% CI 82.6-95.5%) specificity. Importantly, based on mSHOX2 in plasma, lung cancer could be detected with 83.3% (95% CI 65.3-94.4%) sensitivity and 92.6% (95% CI 75.7-99.1%) specificity, respectively. There were insignificant associations between mSHOX2 with age, cancer stage, EGFR mutation and serum CEA, CYFRA21-1 concentrations except for that gender. CONCLUSION: Our study indicated that mSHOX2 was satisfactory for distinguishing malignant from benign lung tissue and noninvasively detecting lung cancer.

Immune Profiling of Combined Hepatocellular- Cholangiocarcinoma Reveals Distinct Subtypes and Activation of Gene Signatures Predictive of Response to Immunotherapy.

PURPOSE: Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a rare malignancy associated with an overall poor prognosis. We aimed to investigate the immune profile of cHCC-CCA and determine its impact on disease outcome. EXPERIMENTAL DESIGN: We performed a multicenter study of 96 patients with cHCC-CCA. Gene expression profile was analyzed using nCounter PanCancer IO 360 Panel. Densities of main immune cells subsets were quantified from digital slides of IHC stainings. Genetic alterations were investigated using targeted next-generation sequencing. RESULTS: Two main immune subtypes of cHCC-CCA were identified by clustering analysis: an "immune-high" (IH) subtype (57% of the cases) and an "immune-low" (IL) subtype (43% of the cases). Tumors classified as IH showed overexpression of genes related to immune cells recruitment, adaptive and innate immunity, antigen presentation, cytotoxicity, immune suppression, and inflammation (P < 0.0001). IH cHCC-CCAs also displayed activation of gene signatures recently shown to be associated with response to immunotherapy in patients with HCC. Quantification of immunostainings confirmed that IH tumors were also characterized by higher densities of immune cells. Immune subtypes were not associated with any genetic alterations. Finally, multivariate analysis showed that the IH subtype was an independent predictor of improved overall survival. CONCLUSIONS: We have identified a subgroup of cHCC-CCA that displays features of an ongoing intratumor immune response, along with an activation of gene signatures predictive of response to immunotherapy in HCC. This tumor subclass is associated with an improved clinical outcome. These findings suggest that a subset of patients with cHCC-CCA may benefit from immunomodulating therapeutic approaches.

The impact of trans-arterial embolization on the result of chemoradiotherapy in oral cavity cancer.

Objectives: Evaluation of the hemostatic effect of trans-arterial embolization on patients with advanced oral cavity cancer who had bleeding complications while undergoing definitive concurrent chemoradiotherapy (CCRT). Additionally, assess the effect of trans-arterial embolization on treatment response following concurrent chemoradiotherapy, as well as overall survival (OS) and progression-free survival (PFS) in the group of patients following the intervention.Method: From September 2018-June 2021, a retrospective descriptive study was conducted on 16 patients with inoperable, locally advanced oral cavity cancer who received definitive concurrent chemoradiotherapy, experienced acute bleeding complications, and received selective intravascular intervention with various embolization materials at Vietnam National Cancer Hospital.Results: After selective embolization, 16/16 patients ceased bleeding; 1 patient re-bled for the second time after 3 weeks. The average duration of chemoradiotherapy interruption due to intervention was 6.7 days. After CCRT, 15/16 (93.75%) patients achieved a response, with 9/16 (56.25%) patients achieving a complete response. The median OS was 14 months (range, 3-26 months), and the median PFS was 10 months (range, 3-20 months). There were no significant complications, particularly neurological side effects.ConclusionsTumor bleeding is a common and serious complication of CCRT treatment in patients with locally advanced oral cavity cancer. Embolization is a safe and effective method of controlling acute bleeding that has no adverse effect on the outcome of definitive concurrent chemoradiotherapy.

External-Beam Radiotherapy Alone Management of Primary CNS Lymphoplasmacytic Lymphoma: A Vietnamese Case Report and Literature Review.

BACKGROUND: Primary central nervous system (CNS) lymphoma is an uncommon non-Hodgkin disease limited to the CNS, and most cases are diffuse large B-cell lymphomas. Other pathologies, including lymphoplasmacytic lymphoma (LPL), are exceedingly rare and poorly understood. The clinical presentation of primary CNS LPL is diverse. It depends on the original site and the tumor's extension. There is currently no consensus on a treatment strategy for this uncommon manifestation. To our knowledge, no previously published case was successfully treated with radiation therapy alone. CASE PRESENTATION: We present here a case of primary CNS LPL. A 46-year-old, previously healthy woman was presented with a worsening headache and lower extremity numbness. Multifocal enhanced masses were detected in an MRI with biopsy results consistent with LPL. A complete staging workup was performed with no evidence of systemic disease. The patient received external-beam radiotherapy alone and had a complete remission. After 2 years of follow-up, she remains disease-free. CONCLUSION: Radiation alone is a promising treatment option for primary CNS lymphoplasmacytic lymphoma.

Promoter methylation profile of GSTP1 and RASSF1A in prostate cancerand benign hyperplasia in Vietnamese men.

BACKGROUND/AIM: The GSTP1 and RASSF1A methylations that were considered as prostate cancer-specific molecular biomarkers have been extensively reported in Western/American patients with prostate cancer but are rarely reported in Southeast Asian patients. In the present study, the methylation status of the GSTP1 and RASSF1A promoters was evaluated in prostate cancer (PCa) and benign prostate hyperplasia (BPH) tissues from Vietnamese men. MATERIALS AND METHODS: The accuracy of methylation-specific polymerase chain reaction (MSP) was validated to analyze the methylation pattern of GSTP1 and RASSF1A in 59 PCa and 37 BPH patients, respectively. The methylation status was confirmed by the sequencing of cloned MSP products. The association between methylation status and the clinical and pathological parameters of tumors was statistically analyzed. RESULTS: The methylation of GSTP1 and RASSF1A was detected in 39/59 and 19/59 PCa patients and in 4/37 and 10/37 BPH patients, respectively. The methylation frequency of GSTP1 was significantly associated with PCa (P < 0.01). The RASSF1A methylation frequency (32.2%) observed in the study was lower relative to that detected in other populations. CONCLUSIONS: GSTP1 and RASSF1A methylation was accurately detected using the validated MSP method and can be used as a biomarker to diagnose prostate cancer.

Mouse mammary tumor virus-like gene sequences in breast tumors of Australian and Vietnamese women.

PURPOSE: There is considerable evidence that the presence of mouse mammary tumor virus (MMTV)-like gene sequences in human breast cancer is highly associated with human breast carcinoma. Previous studies have found MMTV-like gene sequences in 38% of breast cancer tissue from United States women. The prevalence of these sequences in Australian and Vietnamese women has never been reported. EXPERIMENTAL DESIGN: Using PCR and primers that amplify MMTV-like gene sequences, we tested cancerous and benign breast tissue from Caucasian-Australian, Vietnamese-Australian, and Vietnamese women. RESULTS: MMTV-like gene sequences were amplified in 19 of 45 (42.2%) archival breast cancer biopsy tissues from Caucasian-Australian women, but only 1 of 120 (0.8%) and 0 of 41 breast cancer biopsy tissues from Vietnamese and Vietnamese-Australian women, respectively. The same sequences were found in only 2 of 111 (1.8%) and 0 of 60 normal (benign) breast tissue samples from Australian and Vietnamese women, respectively. CONCLUSIONS: MMTV-like gene sequences are found in only some human populations and are rarely found in normal human breast tissue from all populations, suggesting they are not present in the normal human genome and have been acquired.