Elucidation of the molecular pathogenesis of neoplasms and application of emerging technologies for testing and therapy have resulted in a series of paradigm shifts in patient care, from conventional to personalized medicine. This has been promoted by companion diagnostics and molecular targeted therapy, tailoring the treatment to the individual characteristics of each patient. Precision oncology has been accelerated by integrating the enhanced resolution of molecular analysis, mechanism clarity, and therapeutic relevance through genomic knowledge. In its clinical implementation, there are laboratory challenges concerning accurate measurement using stored samples, differentiation between driver and passenger mutations as well as between germline and somatic mutations, bioinformatics availability, practical decision-making algorithms, and ethical issues regarding incidental findings. The medical laboratory has a new role in providing not only testing services but also an instructive approach to users to ensure the sample quality and privacy protection of personal genome information, supporting the quality of patient practice based on laboratory diagnosis.

Targeting of epidermal growth factor receptor (EGFR) with monoclonal antibodies such as cetuximab or panitumumab inhibits the activation of downstream signaling molecules of EGFR. Since EGFR inhibitor therapy has been approved for the treatment of colorectal carcinomas in patients with tumors lacking KRAS mutations, the detection of KRAS mutation is indispensable before starting therapy. Although several laboratory procedures have been developed to detect KRAS mutations, few comparative studies of the sensitivity of mutation detection have been performed for such procedures. Here, we compared the levels of detection in 5 commercial KRAS mutation detection methods using both standard DNA samples and formalin-fixed clinical samples obtained during surgery. Scorpion-ARMS assay has been reported as the most sensitive and we compared 4 other methods with Scorpion. Both PCR-rSSO assay and F-PHFA assay showed the highest concordance. As for the detection sensitivity, there were variations between clinical samples apparently due to sample quality or assay principles and methods. It is thus suggested that routine validation is required using samples prepared in each lab and the choice of assay may depend on various factors, such as lab environment, actual needs of physicians and patients, and the quality of the formalin-fixed specimens.

Human studies suggest that high-fat diets (HFDs) increase the risk of breast cancer. The 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary carcinogenesis rat model is commonly used to evaluate the effects of lifestyle factors such as HFD on mammary tumor risk. Past studies focused primarily on the effects of continuous maternal exposure on the risk of offspring at the end of puberty (PND50). We assessed the effects of prenatal HFD exposure on cancer susceptibility in prepubertal mammary glands and identified key gene networks associated with such disruption. During pregnancy, dams were fed AIN-93G-based diets with isocaloric high olive oil, butterfat or safflower oil. The control group received AIN-93G. Female offspring were treated with DMBA on PND21. However, a significant increase in tumor volume and a trend of shortened tumor latency were observed in rats with HFD exposure against the controls (P=.048 and P=.067, respectively). Large-volume tumors harbored carcinoma in situ. Transcriptome profiling identified 43 differentially expressed genes in the mammary glands of the HFBUTTER group as compared with control. Rapid hormone signaling was the most dysregulated pathway. The diet also induced aberrant expression of Dnmt3a, Mbd1 and Mbd3, consistent with potential epigenetic disruption. Collectively, these findings provide the first evidence supporting susceptibility of prepubertal mammary glands to DMBA-induced tumorigenesis that can be modulated by dietary fat that involves aberrant gene expression and likely epigenetic dysregulation.

Folylpolyglutamate synthase (FPGS) plays a critical role in intracellular folate homeostasis. FPGS-induced polyglutamylated folates are better substrates for several enzymes involved in the generation of S-adenosylmethionine, the primary methyl group donor, and hence FPGS modulation may affect DNA methylation. DNA methylation is an important epigenetic determinant in gene expression and aberrant DNA methylation is mechanistically linked cancer development. We investigated whether FPGS modulation would affect global and gene-specific promoter DNA methylation with consequent functional effects on gene expression profiles in HCT116 colon and MDA-MB-435 breast cancer cells. Although FPGS modulation altered global DNA methylation and DNA methyltransferases (DNMT) activity, the effects of FPGS modulation on global DNA methylation and DNMT activity could not be solely explained by intracellular folate concentrations and content of long-chain folylpolyglutamates, and it may be cell-specific. FPGS modulation influenced differential gene expression and promoter cytosine-guanine dinucleotide sequences (CpG) DNA methylation involved in cellular development, cell cycle, cell death and molecular transport. Some of the altered gene expression was associated with promoter CpG DNA methylation changes. In both the FPGS-overexpressed HCT116 and MDA-MB-435 cell lines, we identified several differentially expressed genes involved in folate biosynthesis and one-carbon metabolism, which might in part have contributed to the observed increased efficacy of 5-fluorouracil in response to FPGS overexpression. Our data suggest that FPGS modulation affects global and promoter CpG DNA methylation and expression of several genes involved in important biological pathways. The potential role of FPGS modulation in DNA methylation and its associated downstream functional effects warrants further studies.

Osteolytic bone disease is a major hallmark in multiple myeloma (MM) progression and affects many patients. Several inflammatory cells are involved in MM progression. Among them, mast cells (MCs) accumulated in the bone marrow (BM) microenvironment are known to play an important role in the mechanism of neovascularization.

To study the expression level and clinical significance of miR-181c-3p and miR-5692b in esophageal cancer.

To study the clinicopathologic features, immunophenotype, differential diagnosis and prognosis of renal cell carcinoma (RCC) associated with t(6;11)(p21.2;q13)/MALAT1-TFEB gene fusion.

To investigate the clinicopathologic features and 19q13.42 gene changes in embryonal tumors with multilayered rosettes (ETMR).

To investigate the clinical utility of short tandem repeats(STR) genotyping technique for diagnosis of partial hydatidiform moles (PHM).

To study the clinicopathologic features of small cell carcinoma of ovary, hypercalcemic type (SCCOHT) and to evaluate the diagnostic significance of loss of SMARCA4 expression.

To investigate the effects of HIF-1α on adhesion and invasion of human nasopharyngeal carcinoma CNE-1 cells under hypoxia and underlying molecular mechanisms.

To investigate the effects of dihydrofolate reductase (DHFR) gene expression up-regulating on cisplatin resistance in epithelial ovarian cancer cell lines.

To investigate the frequeney of four single nucleotide polymorphism (SNP) sites (rs17300539, rs12495941, rs2241766 and rs1501299) of adiponectin gene (ADIPOQ) and to elucidate its role in the pathogenesis of polycystic ovary syndrome (PCOS).

we aimed to investigate the mutation and expression of BRAF gene in mature T/NK cell lymphoma tissues and cell lines, explore the correlation between gene alterations and clinicopathological features and clinical outcomes of mature T/NK cell lymphoma.

Germ-line DICER1 mutations predispose to a distinctive tumour predisposition syndrome, the DICER1 syndrome, which is associated with a spectrum of rare mainly childhood-onset tumours. In 2014, a case of well-differentiated fetal adenocarcinoma of the lung (WDFA) was reported in a 16-year-old germ-line DICER1 mutation carrier. Here we report our finding of a characteristic somatic DICER1 RNase IIIb c.5127T>A (p.Asp1709Glu) missense mutation within the WDFA, confirmed using laser capture microscopy. The child has a personal history consistent with the DICER1 syndrome: she developed a multinodular goitre at age 14 years and an ovarian Sertoli-Leydig cell tumour at age 16 years, each of which were found to harbour a somatic DICER1 RNase IIIb missense mutation. The identification of two DICER1 "hits" in the WDFA strongly suggests that WDFA is a rare, previously-unrecognised manifestation of DICER1 syndrome.

To study the prognosis-predicting value of a risk score based on phosphorylated At (p-Akt), vascular endothelial growth factor (VEGF), and Nin one binding (NOB1) expression in patients with resected non-small-cell lung cancer (NSCLC).

The purpose of this study was to investigate the expression status of Dual-Specificity Phosphatase 5 Pseudogene 1 (DUSP5P1) and its clinical relevance in patients with acute myeloid leukemia (AML). Real-time quantitative PCR (RQ-PCR) was performed to detect the status of DUSP5P1 expression in 89 patients with de novo AML and 24 normal controls. The level of DUSP5P1 expression was significantly up-regulated in AML compared to controls (P=0.031). The patients with high expression of DUSP5P1 had higher percentage of blasts in bone marrow (BM) than those without high expression (P=0.027). The occurrence rate of DUSP5P1 high expression was significantly higher in M1 (2/8, 25%) and M2 subtypes (9/33, 27%) than in M3 subtype (0/17, 0%) (P=0.034). At the same time, the frequency of DUSP5P1 high expression in patients with intermediate (13/53, 24%) and poor karyotypes (5/11, 45%) was significantly higher than that in patients with favorable karyotype (0/21, 0%) (P=0.003). Meanwhile, DUSP5P1 high-expressed patients had significantly shorter overall survival (OS) than those with low expression (median 4.5 vs. 10.5 months, respectively, P=0.038). Our findings indicated that high expression of DUSP5P1 may identify high-risk AML patients and is associated with poor prognosis in AML.