Discovery of novel anaplastic lymphoma kinase (ALK) and histone deacetylase (HDAC) dual inhibitors exhibiting antiproliferative activity against non-small cell lung cancer.

A series of novel benzimidazole derivatives were designed and synthesised based on the structures of reported oral available ALK inhibitor and HDAC inhibitor, pracinostat. In enzymatic assays, compound 3b, containing a 2-acyliminobenzimidazole moiety and hydroxamic acid side chain, could inhibit both ALK and HDAC6 (IC50 = 16 nM and 1.03 µM, respectively). Compound 3b also inhibited various ALK mutants known to be involved in crizotinib resistance, including mutant L1196M (IC50, 4.9 nM). Moreover, 3b inhibited the proliferation of several cancer cell lines, including ALK-addicted H2228 cells. To evaluate its potential for treating cancers in vivo, 3b was used in a human A549 xenograft model with BALB/c nude mice. At 20 mg/kg, 3b inhibited tumour growth by 85% yet had a negligible effect on mean body weight. These results suggest a attracting route for the further research and optimisation of dual ALK/HDAC inhibitors.

Non-homologous End-joining Genotype, mRNA Expression, and DNA Repair Capacity in Childhood Acute Lymphocytic Leukemia.

BACKGROUND/AIM: The capacity for non-homologous end-joining (NHEJ) repair plays a pivotal role in maintaining genome stability and in carcinogenesis. However, there is little literature on the involvement of NHEJ-related genes in childhood acute lymphocytic leukemia (ALL). Our study aimed to elucidate the impact of polymorphisms of X-ray repair cross-complementing group 4 (XRCC4) (rs6869366, rs2075685, rs2075686, rs28360071, rs3734091, rs28360317, rs1805377), XRCC5 (rs828907, rs11685387, rs9288518), XRCC6 (rs5751129, rs2267437, rs132770, rs132774), XRCC7 rs7003908, and DNA ligase IV (LIG4) rs1805388, on the odds of childhood ALL. MATERIALS AND METHODS: Genotypes NHEJ-related genes of 266 cases and 266 controls were determined, and the genotype-phenotype correlation was investigated by examining mRNA transcript expression and the capacity for overall and precise NHEJ repair. RESULTS: The variant genotypes of XRCC4 rs3734091, rs28360071, XRCC5 rs828907, and XRCC6 rs5751129 were significantly associated with increased odds of childhood ALL. Further analysis based on susceptibility genotypes showed no significant differences in mRNA transcript expression levels among childhood ALL cases with various putative high-risk genotypes, except XRCC6 rs5751129. Moreover, the overall NHEJ repair capacity was similar among carriers of different XRCC4, XRCC5, and XRCC6 genotypes. However, it is worth noting that individuals carrying the variant C allele at XRCC6 rs5751129 exhibited lower precise NHEJ repair capacity compared to those with the wild-type T allele. CONCLUSION: Our study identified significant associations between XRCC4 rs3734091, rs28360071, XRCC5 rs828907, and XRCC6 rs5751129 genotypes and childhood ALL. Notably, lower transcriptional expression and reduced precise NHEJ repair capacity were observed in patients carrying the C allele of XRCC6 rs5751129. Further investigations are required to gain deeper insights into childhood ALL development.

Interleukin-8 Rs4073 Genotypes as Prognostic Predictors for Childhood Acute Lymphocytic Leukemia.

BACKGROUND/AIM: Interleukin 8 (IL-8) is highly expressed in refractory acute lymphocytic leukemia (ALL) cells. This study aimed to investigate the contribution of IL-8 polymorphisms to the risk of childhood ALL. MATERIALS AND METHODS: The genotypes of IL-8 rs4073, rs2227306, rs2227543, and rs1126647 were determined in 266 childhood ALL cases and 266 controls using the PCR-RFLP method. Additionally, we assessed whether the interactions of these genotypes with age and sex contributed to childhood ALL risk. RESULTS: The distributions of genotypic and allelic frequencies of IL-8 rs4073, rs2227306, rs2227543, and rs1126647 were not significantly different between childhood ALL cases and controls (all p>0.05). However, carriers of the variant AA genotype at IL-8 rs4073 had a significantly higher risk of childhood ALL among those aged ≤3.5 years and among girls (OR=2.39 and 3.32, 95%CI=1.21-4.73 and 1.51-7.30, p=0.0182 and 0.0042, respectively). In the stratification analysis, IL-8 rs4073 AT and AA genotypes were associated with higher childhood ALL risk classification and shorter survival time (OR=2.21 and 4.13, 95%CI=1.29-3.78 and 1.87-9.10, p=0.0054 and 0.0002, respectively). There was no positive association for rs2227306, rs2227543, or rs1126647 (all p>0.05). CONCLUSION: The A allele of IL-8 rs4073 can serve as a diagnostic predictor for childhood ALL, but only in girls and patients younger than or equal to 3.5 years old. More importantly, it can serve as a prognostic marker for high-risk classification and shorter survival time. Further validation studies can help extend the use of this prognostic predictor in clinical practice.

Exploring the Difficulties and Strategies of Family Caregivers in Caring for Patients With Dementia in Acute Care Wards.

BACKGROUND: Providing appropriate care to patients with dementia in acute care settings can be a challenge for healthcare professionals. A key factor is working closely with family caregivers. PURPOSE: This study aims to explore the difficulties and strategies involved in caring for patients with dementia who have been admitted to an acute care ward from the perspective of family caregivers. METHODS: Exploratory research was conducted using a qualitative data collection approach. Data were collected by means of in-depth interviews carried out with participants. Semistructured interviews were conducted with nine participants. Content analysis was performed to analyze the data. RESULTS: A number of themes and subthemes were identified based on the primary research purposes. The first theme is "vicious cycle due to multiple factors," with the following subthemes: (a) communication disturbance, (b) endless worries, (c) inadequate care skills of paid caregivers, and (d) physical and psychological exhaustion. The second theme is "do everything," with the following subthemes: (a) management of the behavioral and psychological symptoms of dementia, (b) constant accompaniment of the patient, and (c) seeking sources of support. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: The results may be used to help healthcare professionals better anticipate the difficulties faced by family caregivers while providing assistance to patients with dementia and understand the related strategies they use. Acute care wards should consider the specific needs of family caregivers to ensure patients with dementia receive adequate care from the relevant parties in the ecological care chain during the care process.

Significant Contribution of Interleukin-18 Genotypes to Childhood Acute Lymphocytic Leukemia Risk in Taiwanese.

BACKGROUND/AIM: Evidence has shown that interleukin-18 (IL-18) has both antitumor and pro-tumor effects in various types of leukemia. The current study aimed at investigating the contribution of IL-18 polymorphisms to the risk of childhood acute lymphocytic leukemia (ALL) in Taiwan. MATERIALS AND METHODS: IL-18 promoter -656 (rs1946519), -607 (rs1946518), and -137 (rs187238) genotypes of 266 childhood ALL cases and 266 controls were determined by polymerase chain reaction-restriction fragment length polymorphism methodology. RESULTS: The distributions of genotypic and allelic frequencies of IL-18 rs1946519, rs1946518 or rs187238, were not significantly different between childhood ALL cases and controls (all p>0.05). However, in the stratification analysis among the cases, IL-18 rs187238 GC and CC genotypes were associated with increased childhood ALL risk and shorter survival (OR=4.19 and 2.93, 95%CI=2.04-8.64 and 1.19-7.23, p=0.0001 and 0.0250, respectively). No association was found with rs1946519 and rs1946518 (all p>0.05). CONCLUSION: IL-18 rs187238 GC and CC genotypes can serve as predictors for childhood ALL prognosis among Taiwanese. Validation in larger and various populations can greatly extend the feasibility of this novel predictor.

Protective Effects of Jujubosides on 6-OHDA-Induced Neurotoxicity in SH-SY5Y and SK-N-SH Cells.

6-hydroxydopamine (6-OHDA) is used to induce oxidative damage in neuronal cells, which can serve as an experimental model of Parkinson's disease (PD). Jujuboside A and B confer free radical scavenging effects but have never been examined for their neuroprotective effects, especially in PD; therefore, in this study, we aimed to investigate the feasibility of jujubosides as protectors of neurons against 6-OHDA and the underlying mechanisms. 6-OHDA-induced neurotoxicity in the human neuronal cell lines SH-SY5Y and SK-N-SH, was used to evaluate the protective effects of jujubosides. These findings indicated that jujuboside A and B were both capable of rescuing the 6-OHDA-induced loss of cell viability, activation of apoptosis, elevation of reactive oxygen species, and downregulation of the expression levels of superoxide dismutase, catalase, and glutathione peroxidase. In addition, jujuboside A and B can reverse a 6-OHDA-elevated Bax/Bcl-2 ratio, downregulate phosphorylated PI3K and AKT, and activate caspase-3, -7, and -9. These findings showed that jujubosides were capable of protecting both SH-SY5Y and SK-N-SH neuronal cells from 6-OHDA-induced toxicity via the rebalancing of the redox system, together with the resetting of the PI3K/AKT apoptotic signaling cascade. In conclusion, jujuboside may be a potential drug for PD prevention.

Contribution of Cyclin-dependent Kinase Inhibitor 1B Genotypes to Childhood Leukemia Risk.

BACKGROUND/AIM: Although genetic differences in cell-cycle control genes have been associated with cancer risk, to our knowledge, no report has specifically examined the role of gene variants in childhood acute lymphoblastic leukemia (ALL). Cyclin-dependent kinase inhibitor 1B (CDKN1B; also known as p27/KIP1) is a cell-cycle regulating gene. This study aimed at investigating the association between CDKN1B genotypes and childhood ALL risk. MATERIALS AND METHODS: In 266 childhood ALL cases and 266 healthy controls, the CDKN1B rs34330 and 2066827 polymorphisms were genotyped, and the association of CDKN1B genotypes with childhood ALL risk were analyzed. RESULTS: The genotypes of CDKN1B rs34330 and 2066827 were similarly distributed between the control and case groups (p for trend=0.8718 and 0.4030, respectively). The allelic frequency also exhibited no statistical difference (p=1.0000 and 0.6666, respectively). There was no significant interaction between CDKN1B genotypes and age or sex. CONCLUSION: CDKN1B genotypes were not found to be minor contributors to childhood ALL susceptibility in Taiwan.

Exploring the Genetic Architecture of Spontaneous Coronary Artery Dissection Using Whole-Genome Sequencing.

BACKGROUND: Spontaneous coronary artery dissection (SCAD) is a cause of acute coronary syndrome that predominantly affects women. Its pathophysiology remains unclear but connective tissue disorders (CTD) and other vasculopathies have been observed in many SCAD patients. A genetic component for SCAD is increasingly appreciated, although few genes have been robustly implicated. We sought to clarify the genetic cause of SCAD using targeted and genome-wide methods in a cohort of sporadic cases to identify both common and rare disease-associated variants. METHODS: A cohort of 91 unrelated sporadic SCAD cases was investigated for rare, deleterious variants in genes associated with either SCAD or CTD, while new candidate genes were sought using rare variant collapsing analysis and identification of novel loss-of-function variants in genes intolerant to such variation. Finally, 2 SCAD polygenic risk scores were applied to assess the contribution of common variants. RESULTS: We identified 10 cases with at least one rare, likely disease-causing variant in CTD-associated genes, although only one had a CTD phenotype. No genes were significantly associated with SCAD from genome-wide collapsing analysis, however, enrichment for TGF (transforming growth factor)-ß signaling pathway genes was found with analysis of 24 genes harboring novel loss-of-function variants. Both polygenic risk scores demonstrated that sporadic SCAD cases have a significantly elevated genetic SCAD risk compared with controls. CONCLUSIONS: SCAD shares some genetic overlap with CTD, even in the absence of any major CTD phenotype. Consistent with a complex genetic architecture, SCAD patients also have a higher burden of common variants than controls.

Novel Contribution of Long Non-coding RNA MEG3 Genotype to Prediction of Childhood Leukemia Risk.

BACKGROUND/AIM: Acute lymphoblastic leukemia (ALL) is frequent among children. Few studies have researched the relationship between maternally expressed gene 3 (MEG3) and cancer risk. We hypothesized long non-coding RNA MEG3 polymorphisms might influence the risk of childhood ALL. MATERIALS AND METHODS: In a total of 266 patients with childhood ALL and 266 healthy controls, genotypes of MEG3 rs7158663, rs3087918, rs11160608 and rs4081134 single nucleotide polymorphisms were investigated for their associations with childhood ALL. RESULTS: MEG3 rs7158663 AG and AA genotypes were significantly associated with ALL [odds ratio=1.61 (95% confidence interval=1.12-2.31) and 2.21 (1.16-4.22), respectively]. The A allele also exhibited a statistical association with higher risk of ALL (p=0.0015). There was no positive association as for rs3087918, rs11160608 or rs4081134. Interestingly, a significant interaction between MEG3 rs7158663 and age (≥3.5 years) and gender (male) was found. CONCLUSION: MEG3 rs7158663 AG/AA genotypes were associated with higher susceptibility to childhood ALL. These novel findings should be validated in larger populations and different ethnicities.

Significant Association of CCND1 Genotypes With Susceptibility to Childhood Acute Lymphoblastic Leukemia.

BACKGROUND/AIM: This study investigated whether genetic variations in cyclin D1 (CCND1) are associated with susceptibility to childhood acute lymphoblastic leukemia (ALL). MATERIALS AND METHODS: A total of 266 childhood ALL cases and 266 healthy controls were genotyped for CCND1 rs9344 and rs678653. RESULTS: There was a significant difference in the genotypic distribution of rs9344 between childhood ALL patients and healthy controls (p=0.0077). Compared to the AA genotype, AG and GG genotypes were associated with significantly decreased risks of childhood ALL with odds ratio (OR) of 0.65 [95% confidence interval (CI)=0.44-0.94, p=0.0234] and 0.45 (95%CI=0.26-0.78, p=0.0040), respectively. Supporting this, allelic frequency distributions between childhood ALL patients and controls was significantly different (OR=0.68, 95%CI=0.53-0.88, p=0.0025). There was no significant difference in the genotypic and allelic distributions of rs678653 between cases and controls. CONCLUSION: CCND1 rs9344, but not rs678653, may serve as a predictive marker of susceptibility for childhood ALL.

Effectiveness of a Sexual Health Care Training to Enhance Psychiatric Nurses' Knowledge, Attitude, and Self-Efficacy: A Quasi-Experimental Study in Southern Taiwan.

BACKGROUND: Sexual health is a taboo issue in some societies. Limited assessments were conducted during nursing care in mental health services. It is unknown whether psychiatric nurses' competencies would be enhanced through short training courses. OBJECTIVE: The present study employed a quasi-experimental design to evaluate the effectiveness of an 8-hour sexual health care training for psychiatric nurses to improve sexual health knowledge, attitude, and self-efficacy in a teaching psychiatric hospital in southern Taiwan. METHOD: Volunteered psychiatric nurses were randomly assigned to the experimental or control group. The 8-hour training program contained sexual health knowledge and attitudes, case discussion, role play, and sexual identity or harassment issues. Each nurse received a pretest and a posttest in the 1-month period between August and September 2019. Descriptive and multivariate statistical analyses were used to evaluate the effects. RESULTS: Among the 75 psychiatric nurses, 43 were in the control group and 32 were in the experimental group. The two groups were not significantly different in the working year, gender, education, marriage, and other psychosocial variables. After the training, the overall performance of sexual health care knowledge, attitudes, and self-efficacy of the experimental group improved significantly than the controls. CONCLUSIONS: The sexual health care training program enhanced psychiatric nurses' confidence and generally improved their sexual knowledge and attitudes. It is suggested that sexual health care needs to be highlighted during in-job training to augment the well-being and life quality of psychiatric patients.

[Needs, Dilemmas, and Policy Suggestions Related to Patients With Mental Health Long-Term Care].

In Taiwan, The increase in life expectancy in Taiwan has increased the incidents of age-related problems among patients with mental illness. Therefore, the needs related to long-term care in mental health are significantly important. These needs include: (1) reducing stigmatization; (2) reducing the physical and economic burden of caregivers; (3) constructing a comprehensive, long-term care service system; and (4) developing assessment tools suitable to the long-term care of patients with mental illness. Moreover, six dilemmas in meeting long-term care needs were identified. These dilemmas include: (1) lack of a model of continuous care and of a platform for integrating hospital and community resources; (2) poor / inadequate service quality provided by certain community rehabilitation institutions; (3) the needs of patient/family centered care; (4) the persistence of stigma and misunderstanding; (5) the heavy burdens borne by family members providing long-term care; and (6) the disconnect between subsequent needs and the disability assessment system. Policy suggestions provided in this article include: (1) establish an inclusive platform for mental health long-term care information and resource integration; (2) construct long-term care centers for patients with mental health conditions; (3) train adequate manpower to provide long-term care services to these patients; and (4) promote community inclusiveness for these patients. In order to enter the era of long-term mental health care, government policy should target long-term care programs to meet the needs of patients with mental health conditions. These programs should include seamlessly integrating services into the long-term mental health care system and the care resources of community mental health, developing suitable assessment tools, establishing a multidisciplinary team of long-term care professionals to provide mental health care.

Significant Associations of lncRNA H19 Genotypes with Susceptibility to Childhood Leukemia in Taiwan.

The purpose of our study was to investigate whether genetic variations in lncRNA H19 were associated with susceptibility to childhood leukemia. Two hundred and sixty-six childhood leukemia patients and 266 healthy controls were enrolled in Taiwan, and two single nucleotide polymorphisms (SNPs), rs2839698 and rs217727, in H19 were genotyped and analyzed. There was a significant difference in the genotypic distribution of rs2839698 between patients and healthy controls (p = 0.0277). Compared to the wild-type CC genotype, the heterozygous variant CT and homozygous variant TT genotypes were associated with significantly increased risks of childhood leukemia with an adjusted odd ratio (OR) of 1.46 (95% confidence interval (CI), 1.08-2.14, p = 0.0429) and 1.94 (95%CI, 1.15-3.31, p = 0.0169), respectively (pfor tread = 0.0277). The difference in allelic frequencies between childhood leukemia patients and controls was also significant (T versus C, adjusted OR = 1.53, 95%CI, 1.13-1.79, p = 0.0077). There were no significant differences in the genotypic and allelic distributions of rs217727 between cases and controls. Interestingly, the average level of H19 rs2839698 was statistically significantly higher for patients with CT and TT genotypes than from those with the CC genotype (p < 0.0001). Our results indicate that H19 SNP rs2839698, but not rs217727, may serve as a novel susceptibility marker for childhood leukemia.

MiR-196a-2 Genotypes Determine the Susceptibility and Early Onset of Childhood Acute Lymphoblastic Leukemia.

BACKGROUND/AIM: The roles of microRNAs (miRNAs) in tumorigenesis have attracted a lot of attention. The current study aimed at examining the association of the miR-196a-2 rs11614913 genotypes with susceptibility to childhood acute lymphoblastic leukemia (ALL) in Taiwan. MATERIALS AND METHODS: This case-control investigation recruited 266 patients with childhood ALL and 266 healthy controls, and the miR-196a-2 rs11614913 genotypes of each participant were examined via the polymerase chain reaction-restriction fragment length polymorphism methodology. RESULTS: The frequency of miR-196a-2 C allele in controls was 0.440 compared with 0.423 in ALL patients. In addition, there was no significant association between CT or CC genotypes with susceptibility to childhood ALL (OR=0.89 and 0.89, 95%CI=0.60-1.30 and 0.54-1.45, p=0.5427 and 0.6302). Furthermore, the frequencies of miR-196a-2 polymorphisms were not associated with age, gender and clinical outcomes in ALL cases. CONCLUSION: The miR-19a-2 genotypes are not associated with susceptibility to childhood ALL in Taiwan.

Protective effects of valproic acid on 6-hydroxydopamine-induced neuroinjury.

Oxidative stress may play critically important roles in the etiology of Parkinson's disease (PD). 6-Hydroxydopamine (6-OHDA) is a physiological neurotoxin reported to induce oxidative-induced apoptosis of dopaminergic neurons in PD mice models. Valproic acid (VPA), a clinical mood stabilizer, is a HDAC inhibitor with neuroprotective capacities. In the study, we aim at examining the feasibility of VPA as a protector for dopaminergic neurons against damage from 6-OHDA, and the intracellular mechanisms. The 6-OHDA-induced neurotoxicity to the human dopaminergic cell line SH-SY5Y was applied for examining VPA protective effects. Pretreatment with VPA was able to improve cell viability and reduce 6-OHDA-induced reactive oxygen species. Furthermore, a significant suppression of apoptotic caspases including cleaved caspase-3, caspase-7, and caspase-9 was observed. The results also revealed VPA decreased the 6-OHDA-induced Bax/Bcl2 ratio, as measured at protein level. These novel findings indicate that VPA may be capable of protecting the SH-SY5Y dopaminergic neuronal cells from 6-OHDA-induced toxicity via the deceasing of apoptotic caspases (cleaved caspase-3, caspase-7, and caspase-9) and reducing of the Bax/Bcl2 ratio. Very possibly, VPA could serve as not only a mood stabilizer but also a potential antidote for PD prevention.

Significant Association Between the MiR146a Genotypes and Susceptibility to Childhood Acute Lymphoblastic Leukemia in Taiwan.

BACKGROUND/AIM: Mounting evidence has shown that miRNAs play a critical role in the regulation of hematopoiesis of cell proliferation and apoptosis as well as in tumorigenesis. The miR146a rs2910164 polymorphism, which is closely responsive for its expression, has been reported to associate with the risk of several solid cancers. The study aimed at examining the association of the it with susceptibility to childhood acute lymphoblastic leukemia (ALL) in Taiwan. MATERIALS AND METHODS: We recruited 266 patients with childhood ALL and 266 healthy controls, and rs2910164 genotypes were determined by the polymerase chain reaction-restriction fragment length polymorphism methodology. RESULTS: The allele G was associated with decreased childhood ALL risk (OR=0.66, 95%CI=0.52-0.85, p=0.0011). Consistently, the GG genotype was associated with a decreased susceptibility (OR=0.40, 95%CI=0.23-0.67, p=0.0004). Patients with CG and GG genotypes were of earlier onset than those with CC genotype (p=0.0255 and p=0.0001). CONCLUSION: MiR146a rs2910164 G allele serves as a protective marker for childhood ALL in Taiwan.

An improved core-shell microcapsule diet for rearing larvae of Mallada basalis (Neuroptera: Chrysopidae).

BACKGROUND: Green lacewings (Neuroptera: Chrysopidae) are important beneficial insects that can be raised on artificial diets for culturing experimental lines. An encapsulation method for embedding a core material within a sealed shell to prevent evaporation and biological contamination is crucial for providing food to these predatory insects. RESULTS: This study presents a new encapsulation process to mass produce a core-shell microcapsule diet for rearing Mallada basalis (Walker) (Neuroptera: Chrysopidae). This new process provided consistent quality control and effectiveness of the microcapsule diet (742.1 ± 11.3 µm in diameter and 44.2 ± 1.9 µm in shell thickness). Furthermore, significant differences were measured in larval development (24.0 ± 0.3 vs. 20.1 ± 0.6 days) and fecundity (465 ± 65.05 vs. 678 ± 54.91 eggs) on comparing the development of M. basalis larvae fed the old and new diets. Survival rates increased in both single- and group-rearing tests for adults fed the new diet during the larval stages. Neither diet affected predation rates for M. basalis larvae preying on nymphs of Aphis gossypii Glover (Hemiptera: Aphididae) and Bemisia argentifolli Bellows and Perring (Hemiptera: Aleyrodidae). CONCLUSION: Compared with the old process, the new encapsulation process requires reduced effort during preparation, and reduces the weight, cost and space occupied by the equipment. The results of this study suggest that this new spherical microcapsule artificial diet is suitable for group-rearing of M. basalis and may be appropriate for mass-rearing of other types of carnivorous insects. © 2019 Society of Chemical Industry.

Comparison of somatic variant detection algorithms using Ion Torrent targeted deep sequencing data.

BACKGROUND: The application of next-generation sequencing in cancer has revealed the genomic landscape of many tumour types and is nowadays routinely used in research and clinical settings. Multiple algorithms have been developed to detect somatic variation from sequencing data using either paired tumour-blood or tumour-only samples. Most of these methods have been developed and evaluated for the identification of somatic variation using Illumina sequencing datasets of moderate coverage. However, a comprehensive evaluation of somatic variant detection algorithms on Ion Torrent targeted deep sequencing data has not been performed. METHODS: We have applied three somatic detection algorithms, Torrent Variant Caller, MuTect2 and VarScan2, on a large cohort of ovarian cancer patients comprising of 208 paired tumour-blood samples and 253 tumour-only samples sequenced deeply on Ion Torrent Proton platform across 330 amplicons. Subsequently, the concordance and performance of the three somatic variant callers were assessed. RESULTS: We have observed low concordance across the algorithms with only 0.5% of SNV and 0.02% of INDEL calls in common across all three methods. The intersection of all methods showed better performance when assessed using correlation with known mutational signatures, overlap with COSMIC variation and by examining the variant characteristics. The Torrent Variant Caller also performed well with the advantage of not eliminating a high number of variants that could lead to high type II error. CONCLUSIONS: Our results suggest that caution should be taken when applying state-of-the-art somatic variant algorithms to Ion Torrent targeted deep sequencing data. Better quality control procedures and strategies that combine results from multiple methods should ensure that higher accuracy is achieved. This is essential to ensure that results from bioinformatics pipelines using Ion Torrent deep sequencing can be robustly applied in cancer research and in the clinic.

HOGG1 rs1052133 Genotypes and Risk of Childhood Acute Lymphoblastic Leukemia in a Taiwanese Population.

BACKGROUND/AIM: Cells suffer from oxidative DNA damage which leads to the accumulation of 8-oxoguanine (8-oxoG) adducts in our genome that can become carcinogenic. The human 8-oxoG DNA glycosylase 1 (hOGG1) plays a central role in repairing these 8-oxoGs via the base excision repair pathway. Mounting evidence has suggested that hOGG1 polymorphisms may affect the activity of hOGG1 and serve as genomic markers for the prediction of personal susceptibility to several cancers. To determine whether the commonly examined hOGG1 rs1052133 (Ser326Cys) polymorphism is associated with the risk of childhood acute lymphoblastic leukemia (ALL) among Taiwanese children, we genotyped the hOGG1 rs1052133 (Ser326Cys) in 266 cases and 266 controls. RESULTS: The distributions of the GG, CG and CC genotypes at the hOGG1 rs1052133 were 49.2, 39.1 and 11.7% in the control group and 48.1, 36.1 and 15.8% in the case group (p=0.3656). The combined genotypes CG+CC were not associated with increased risk of childhood ALL (odds ratio [OR]=1.05, 95% confidence interval [CI]=0.74-1.47, p=0.7947). CONCLUSION: The hOGG1 rs1052133 polymorphism is not associated with susceptibility to childhood ALL in the Taiwanese population.

Association of Matrix Metallopeptidase-2 Promoter Polymorphisms With the Risk of Childhood Leukemia.

BACKGROUND/AIM: The association of matrix metalloproteinase-2 (MMP-2) genotypes with adult leukemia has been reported only once, but never for childhood leukemia. This study aimed to determine the role of MMP-2 promoter -1306 (rs243865) and -735 (rs2285053) genotypes in childhood leukemia risk. MATERIALS AND METHODS: This case-control study included 266 patients and 266 age- and gender-matched healthy controls. The polymorphic sites of MMP-2 were genotyped by typical polymerase chain reaction-restriction fragment length polymorphism. RESULTS: The CC, CT and TT of rs243865 genotype were 75.2, 23.7 and 1.1% in the case group and 69.2, 28.9 and 1.9% in the control group, respectively. The CT and TT genotypes caused a 0.75- and 0.55-fold increase in the risk of childhood leukemia, respectively. There was no differential distribution of rs2285053 genotypes. Allelic frequency analysis showed that the T allele of MMP-2 promoter -1306 and -735 conferred lower susceptibility than the C allele. CONCLUSION: The MMP-2 promoter genotypes play a minor role in determining personal susceptibility to childhood leukemia among the Taiwanese.