Background To validate the clinical application of chromosomal microarray analysis (CMA) as a first-tier clinical diagnostic test and to determine the impact of CMA results on patient clinical management, we conducted a multicenter prospective study in Korean patients diagnosed as having developmental delay/intellectual disability (DD/ID), autism spectrum disorders (ASD), and multiple congenital anomalies (MCA). Methods We performed both CMA and G-banding cytogenetics as the first-tier tests in 617 patients. To determine whether the CMA results directly influenced treatment recommendations, the referring clinicians were asked to complete a 39-item questionnaire for each patient separately after receiving the CMA results. Results A total of 122 patients (19.8%) had abnormal CMA results, with either pathogenic variants (N=65) or variants of possible significance (VPS, N=57). Thirty-five well-known diseases were detected: 16p11.2 microdeletion syndrome was the most common, followed by Prader-Willi syndrome, 15q11-q13 duplication, Down syndrome, and Duchenne muscular dystrophy. Variants of unknown significance (VUS) were discovered in 51 patients (8.3%). VUS of genes putatively associated with developmental disorders were found in five patients: IMMP2L deletion, PTCH1 duplication, and ATRNL1 deletion. CMA results influenced clinical management, such as imaging studies, specialist referral, and laboratory testing in 71.4% of patients overall, and in 86.0%, 83.3%, 75.0%, and 67.3% of patients with VPS, pathogenic variants, VUS, and benign variants, respectively. Conclusions Clinical application of CMA as a first-tier test improves diagnostic yields and the quality of clinical management in patients with DD/ID, ASD, and MCA.

AbstractsBackgroundsVarious studies have reported that the neutrophil-to-lymphocyte ratio in the serum (sNLR) may serve as a cost-effective and useful prognostic factor in patients with various cancer types. However, no study has reported the prognostic impact of the NLR in malignant pleural effusion (MPE). To address this gap, we investigated the clinical impact of NLR as a prognostic factor in MPE (mNLR) and a new scoring system that use NLRs in the serum and MPE (smNLR score) in lung cancer patients.MethodsWe retrospectively reviewed all of the patients who were diagnosed with lung cancer and who presented with pleural effusion. To maintain the quality of the study, only patients with malignant cells in the pleural fluid or tissue were included. The patients were classified into three smNLR score groups, and clinical variables were investigated for their correlation with survival.ResultsIn all, 158 patients were classified into three smNLR score groups as follows: 84 (53.2%) had a score of 0, 58 (36.7%) had a score of 1, and 16 (10.1%) had a score of 2. In a univariate analysis, high sNLR, mNLR, and increments of the smNLR score were associated with shorter overall survival (p < 0.001, p = 0.004, and p < 0.001, respectively); moreover, age, Eastern Cooperative Oncology Group performance status (ECOG PS), histology, M stage, hemoglobin level, albumin level, and calcium level were significant prognostic factors. A multivariable analysis confirmed that ECOG PS (p < 0.001), histology (p = 0.001), and smNLR score (p < 0.012) were independent predictors of overall survival.ConclusionsThe new smNLR score is a useful and cost-effective prognostic factor in lung cancer patients with MPE. Although further studies are required to generalize our results, this information will benefit clinicians and patients in determining the most appropriate therapy for patients with MPE.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-017-3550-8) contains supplementary material, which is available to authorized users.

Background : The in vivo skin prick test (SPT) or in vitro detection of allergen specific IgE in serum is commonly used for the diagnosis of allergic disease. In this study, we evaluated the usefulness of a new multiple allergen simultaneous test (MAST) immunoblot assay, Polycheck Allergy (Biocheck GmbH, Germany).Methods : A total of 100 patients with clinical findings of allergic diseases were tested by SPT and three different MAST assays: Polycheck Allergy (Biocheck GmbH, Germany), MAST CLA allergy system (Hitachi Chemical Diagnostics, USA) and Allergy Screen (R-biopharm, Germany). The results of MAST assays were compared with those of SPT.Results : Concordance rates of MAST assays with SPT were 79-100% for Polycheck Allergy, 88.9-100% for MAST CLA and 72.7-98.3% for Allergy Screen. In ROC curve analysis, significant differences were observed in four of 25 allergens analysed: Alternaria, Birch, Hazelnut and D. farinae. For Alternaria and Birch, Polycheck Allergy (P<0.001) and Allergy Screen (P=0.0075) showed significantly larger AUC (area under the curve) than MAST CLA. For Hazelnut, Polycheck Allergy (P=0.0021), and for D. farinae, MAST CLA (P=0.015) showed significantly larger AUCs than the other two tests. The ROC analysis for overall 16 food allergens showed better results in Polycheck Allergy (P<0.001), and that for overall 21 inhalants did not show significant differences among three MAST assays (P>0.05).Conclusions : Since Polycheck Allergy showed similar or superior result to the others, it can be used for the detection of allergen specific IgE antibodies. (Korean J Lab Med 2009;29:465-72)

Key Points• MN1 promotes self-renewal and inhibits differentiation of CD34 1 cord blood cells in vitro.• De novo leukemogenesis is engineered by MN1 and NUP98HOXD13 expression in cord blood cells.

Extensive molecular profiling of leukemias and preleukemic diseases has revealed that distinct clinical entities, like acute myeloid (AML) and T-lymphoblastic leukemia (T-ALL), share similar pathogenetic mutations. It is not well understood how the cell of origin, accompanying mutations, extracellular signals or structural differences in a mutated gene determine the phenotypic identity of leukemias. We dissected the functional aspects of different protein regions of the MN1 oncogene and their effect on the leukemic phenotype, building on the ability of MN1 to induce leukemia without accompanying mutations. We found that the most C-terminal region of MN1 was required to block myeloid differentiation at an early stage, and deletion of an extended C-terminal region resulted in loss of myeloid identity and cell differentiation along the T-cell lineage in vivo. Megakaryocytic/erythroid lineage differentiation was blocked by the N-terminal region. In addition, the N-terminus was required for proliferation and leukemogenesis in vitro and in vivo through upregulation of HoxA9, HoxA10 and Meis2. Our results provide evidence that a single oncogene can modulate cellular identity of leukemic cells based on its active gene regions. It is therefore likely that different mutations in the same oncogene may impact cell fate decisions and phenotypic appearance of malignant diseases.