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Here, we announce the draft genome sequence of a Candida parapsilosis clinical isolate (USM039K) recovered from a patient with catheter-related bloodstream infection (CRBSI). The genome size is 12,860,016 bp long, with 188 scaffolds, a G+C content of 38.65%, and 5,467 genes.

Background: This study aimed to identify new genes associated with CRC in patients with normal mismatch repair (MMR) protein expression. Method: Whole-genome sequencing (WGS) was performed in seven early-age-onset Malay CRC patients. Potential germline genetic variants, including single-nucleotide variations and insertions and deletions (indels), were prioritized using functional and predictive algorithms. Results: An average of 3.2 million single-nucleotide variations (SNVs) and over 800 indels were identified. Three potential candidate variants in three genes—IFNE, PTCH2 and SEMA3D—which were predicted to affect protein function, were identified in three Malay CRC patients. In addition, 19 candidate genes—ANKDD1B, CENPM, CLDN5, MAGEB16, MAP3K14, MOB3C, MS4A12, MUC19, OR2L8, OR51Q1, OR51AR1, PDE4DIP, PKD1L3, PRIM2, PRM3, SEC22B, TPTE, USP29 and ZNF117—harbouring nonsense variants were prioritised. These genes are suggested to play a role in cancer predisposition and to be associated with cancer risk. Pathway enrichment analysis indicated significant enrichment in the olfactory signalling pathway. Conclusion: This study provides a new spectrum of insights into the potential genes, variants and pathways associated with CRC in Malay patients.

BACKGROUND Hereditary nonpolyposis colorectal cancer, or Lynch syndrome, caused by germline mutations or genetic defects in mismatch repair (MMR) genes (MLH1, MSH2, PMS2, MSH6, and epithelial cellular adhesion molecule), is an autosomal dominant condition accounting for 2–5% of all colorectal carcinomas (CRCs). Reports on MMR loss in many populations are available; however, there are no reports on the frequency of MMR protein expression in Nepalese cohorts. Therefore, this study was aimed to assess the expression profiles of MLH1 and MSH2 protein by immunohistochemistry (IHC) in Nepalese CRC patients. METHODS This retrospective study used archived formalin-fixed paraffin-embedded tissue blocks from 43 Nepalese CRC patients. IHC staining was performed using MLH1 and MSH2 antibodies. IHC scoring analysis was assessed using semiquantitative scoring. RESULTS Of the 43 CRC patients, 8 (18.6%) showed loss of staining for MLH1 antibody, 5 (11.6%) showed loss of staining for MSH2 antibody, and 4 (9.3%) showed loss of staining for both MLH1 and MSH2 antibodies. CONCLUSIONS IHC is a potential screening method of determining the MMR expression profile of Nepalese CRC patients. IHC can be performed in local clinical laboratories to find MMR protein defects in selected cases prior to expensive molecular tests.

Management of nasopharyngeal carcinoma (NPC) remains elusive despite new developments and advancement that has been made in the current management approaches. A patient’s survival and prognosis remain dismal especially for a late-stage disease. This is highly attribute to the chemoradiation resistance. Arrays of genes and molecular mechanisms underlie the development of chemoradiation resistance in NPC. Imperatively, unravelling the true pathogenesis of chemoradiation resistance is crucial as these significant proteins and genes can be modulated to produce an effective therapeutic target. It is pivotal to identify the chemoradiation resistance at the very beginning in order to combat the chemoradiation resistance efficiently. Intense research in the genetic ecosphere is critical, as the discovery and development of novel therapeutic targets can be used for screening, diagnosis, and treating the chemoradiation resistance aggressively. This will escalate the management trajectory of NPC patients. This article highlights the significance of genetic and molecular factors that play critical roles in the chemoradiation resistance and how these factors may be modified for next-generation targeted therapy products.

Background: Hereditary nonpolyposis colorectal cancer (HNPCC) also known as Lynch syndrome is commonly caused by genetic alterations in any of the four mismatch repair (MMR) genes; MLH1, MSH2, MSH6 and PMS2. This is the first study aimed to investigate genetic variants in Malay HNPCC families. Methods: Six Malay HNPCC families who fulfilled any of the Bethesda criteria were recruited into this study. A total of 3 ml of blood was withdrawn from each patient in the families. The samples were further analyzed using polymerase chain reaction and direct sequencing of the selected exons of MLH1 and MSH2 genes. Results: Two missense mutations and four single nucleotide polymorphisms (SNPs) were identified in six patients. These variants in the MLH1 and MSH2 genes were identified in four families who met the revised Bethesda guidelines. In two families, no mutation and polymorphism was identified in both the exon and intron of the respective genes. Of the mutations and polymorphisms identified, five have never been reported in Malay HNPCC families before. A missense mutation was detected in exon 5 of the MLH1 gene, c.394G>C (p.Asp132His) and four mutations and polymorphisms were detected in the MSH2 gene; heterozygous c.211+98T>C and c.211+9C>G and homozygous c.211+98T>C and c.211+9C>G, c.367-86A>C and c.382C>G. Conclusion: The results represented a new spectrum of mutations and polymorphisms in the Malay HNPCC families. However, a larger study involving additional families and analysis is required to determine the impact and nature of the identified mutations and polymorphisms.

BACKGROUND: Lynch syndrome (LS) is an inherited predisposition to colorectal, endometrial (uterine) and other cancers. Although most cancers are not inherited, about 5 percent (%) of people who have colorectal or endometrial cancer have the Lynch syndrome. It involves the alteration of mismatch repair (MMR) genes; MLH1, MSH2, MSH6 or PMS2. In this study, we analyzed the expression of MMR proteins in colorectal cancer in a Malay cohort by immunohistochemistry. MATERIALS AND METHODS: A total of 17 patients were selected fulfilling one of the Bethesda criteria: colorectal cancer diagnosed in a patient aged less than 50 years old, having synchronous and metachronous colorectal cancer or with a strong family history. Immunohistochemical staining was performed on paraffin embedded tumour tissue samples using four antibodies: MLH1, MSH2, MSH6 and PMS2. RESULTS: Twelve out of 17 patients (70.6%) were noted to have a family history. A total of 41% (n=7) of the patients had abnormal immunohistochemical staining with one or more of the four antibodies. Loss of expression were noted in 13 tumour tissues with a negative staining score

Hemoglobinopathies are among the most common autosomal-recessive disorders worldwide. A comprehensive next-generation sequencing (NGS) test would greatly facilitate screening and diagnosis of these disorders. An NGS panel targeting the coding regions of hemoglobin genes and four modifier genes was designed. We validated the assay by using 2522 subjects affected with hemoglobinopathies and applied it to carrier testing in a cohort of 10,111 couples who were also screened through traditional methods. In the clinical genotyping analysis of 1182 β-thalassemia subjects, we identified a group of additional variants that can be used for accurate diagnosis. In the molecular screening analysis of the 10,111 couples, we detected 4180 individuals in total who carried 4840 mutant alleles, and identified 186 couples at risk of having affected offspring. 12.1% of the pathogenic or likely pathogenic variants identified by our NGS assay, which were undetectable by traditional methods. Compared with the traditional methods, our assay identified an additional at-risk 35 couples. We describe a comprehensive NGS-based test that offers advantages over the traditional screening/molecular testing methods. To our knowledge, this is among the first large-scale population study to systematically evaluate the application of an NGS technique in carrier screening and molecular diagnosis of hemoglobinopathies., Highlights • In 10,111 couples in prevention programs for thalassemia, 186 at-risk couples were identified by NGS and 151 by traditional routine method. • NGS assay had better performance than traditional routine screening approach in carrier screening for hemoglobinopathies. • NGS assay can characterize patients with Thalassemia Major or Thalassemia Intermedia more accurately. Hemoglobinopathies represent a major cause of birth defects in China. Traditional carrier screening strategy is phenotype-based that is associated with risk of miss phenotype-negative carriers. In this study, we validated an effective method for molecular screening and clinical genotyping of hemoglobinopathies using NGS assay. Considering the broad mutation spectrum and high prevalence of hemoglobinopathy-causing mutations across ethnic groups, this technology could make it technically feasible to offer more effective preconception screening and diagnosis in large populations worldwide. Therefore, the current phenotype-based screening guideline might be modified to a better genotype-based screening guideline.

BackgroundThe sequencing of two members of the Royal Kelantan Malay family genomes will provide insights on the Kelantan Malay whole genome sequences. The two Kelantan Malay genomes were analyzed for the SNP markers associated with thalassemia andHelicobacter pyloriinfection.Helicobacter pyloriinfection was reported to be low prevalence in the north-east as compared to the west coast of the Peninsular Malaysia and beta-thalassemia was known to be one of the most common inherited and genetic disorder in Malaysia.ResultBy combining SNP information from literatures, GWAS study and NCBI ClinVar, 18 unique SNPs were selected for further analysis. From these 18 SNPs, 10 SNPs came from previous study ofHelicobacter pyloriinfection among Malay patients, 6 SNPs were from NCBI ClinVar and 2 SNPs from GWAS studies. The analysis reveals that both Royal Kelantan Malay genomes shared all the 10 SNPs identified by Maran (Single Nucleotide Polymorphims (SNPs) genotypic profiling of Malay patients with and without Helicobacter pylori infection in Kelantan, 2011) and one SNP from GWAS study. In addition, the analysis also reveals that both Royal Kelantan Malay genomes shared 3 SNP markers; HBG1 (rs1061234), HBB (rs1609812) and BCL11A (rs766432) where all three markers were associated with beta-thalassemia.ConclusionsOur findings suggest that the Royal Kelantan Malays carry the SNPs which are associated with protection toHelicobacter pyloriinfection. In addition they also carry SNPs which are associated with beta-thalassemia. These findings are in line with the findings by other researchers who conducted studies on thalassemia andHelicobacter pyloriinfection in the non-royal Malay population.