Pan-cancer Analysis of Tumor Mutational Burden and Homologous Recombination DNA Damage Repair Using Targeted Next-Generation Sequencing / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Current variability in methods for tumor mutational burden (TMB) estimation and reporting demonstrates the urgent need for a homogeneous TMB assessment approach. Here, we compared TMB distributions in different cancer types using two customized targeted panels commonly used in clinical practice. @*Materials and Methods@#TMB spectra of 295- and 1021-gene panels in multiple cancer types were compared using targeted next-generation sequencing (NGS). The TMB distributions across a diverse cohort of 2,332 cancer cases were then investigated for their associations with clinical features. Treatment response data were collected for 222 patients who received immune-checkpoint inhibitors (ICIs) and their homologous recombination DNA damage repair (HR-DDR) and programmed death-ligand 1 (PD-L1) expression were additionally assessed and compared with the TMB and response rate. @*Results@#The median TMB between gene panels was similar despite a wide range in TMB values. The highest TMB was 8 and 10 in patients with squamous cell carcinoma and esophageal carcinoma according to the classification of histopathology and cancer types, respectively. Twenty-three out of 103 patients (22.3%) were HR-DDR‒positive and could benefit from ICI therapy; out of those 23 patients, seven patients had high TMB (p=0.004). Additionally, PD-L1 expression was not associated with TMB or treatment response among patients receiving ICIs. @*Conclusion@#Targeted NGS assays demonstrated the ability to evaluate TMB in pan-cancer samples as a tool to predict response to ICIs. In addition, TMB integrated with HR-DDR‒positive status could be a significant biomarker for predicting ICI response in patients.

The clinical relevance of MBL2 gene polymorphism and sepsis

Objective:To detect the clinical relevance of mannose-binding lectin 2 (MBL2) gene polymorphism and sepsis in Chinese lived in Hainan island.Methods:Blood samples from 57 patients with sepsis and 69 patients without sepsis were collected in the ICU of several large hospitals in Hainan province. Genomic DNA was extracted from whole blood and then PCR purification product was sequenced and typed by 3730 sequencing analyzer. The concentration of MBL2 in serum was detected by ELISA.Results:We found that genotype and allele distributions in two groups were in accordance with the Hardy-Weinberg Equilibrium. The frequency of GA genotype was significantly higher than that in non-sepsis group (P=0.013). A allele frequency in sepsis group was also much higher than that in non-sepsis group (P=0.028). Logister regression analysis showed that the patients who carried A allele were more prone to get sepsis than G allele carrier (P=0.014, 0R=2.550, 95%CI=1.207-5.386). The MBL2 level in serum of sepsis patients with genotype GG and GA was significantly lower than that in non-sepsis group (P<0.05). In sepsis group, the MBL2 serum level of patients with genotype GA was obviously lower than that in patients with genotype GG (P<0.05).Conclusions:The variation of rs1800450 G→A increased the incidence of sepsis and decreased the level of MBL2 in serum.

The clinical relevance of MBL2 gene polymorphism and sepsis

Objective: To detect the clinical relevance of mannose-binding lectin 2 (MBL2) gene polymorphism and sepsis in Chinese lived in Hainan island. Methods: Blood samples from 57 patients with sepsis and 69 patients without sepsis were collected in the ICU of several large hospitals in Hainan province. Genomic DNA was extracted from whole blood and then PCR purification product was sequenced and typed by 3730 sequencing analyzer. The concentration of MBL2 in serum was detected by ELISA. Results: We found that genotype and allele distributions in two groups were in accordance with the Hardy-Weinberg Equilibrium. The frequency of GA genotype was significantly higher than that in non-sepsis group (P=0.013). A allele frequency in sepsis group was also much higher than that in non-sepsis group (P=0.028). Logister regression analysis showed that the patients who carried A allele were more prone to get sepsis than G allele carrier (P=0.014, 0R=2.550, 95%CI=1.207-5.386). The MBL2 level in serum of sepsis patients with genotype GG and GA was significantly lower than that in non-sepsis group (P<0.05). In sepsis group, the MBL2 serum level of patients with genotype GA was obviously lower than that in patients with genotype GG (P<0.05). Conclusions: The variation of rs1800450 G→A increased the incidence of sepsis and decreased the level of MBL2 in serum.