• bone marrow
• bone metastasis
• disseminated tumour cells
• metastastic mechanisms

• allelic imbalance
• copy number alterations
• heterogeneous DNA
• loss of heterozygosity
• matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF) mass spectrometry

• Carcinoma
• DNA
• DNA Copy Number Variations
• Humans
• Lasers
• Polymorphism, Single Nucleotide
• Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Drug development often relies on high-throughput cell-based screening of large compound libraries. However, the lack of miniaturized and parallelized methodologies in chemistry as well as strict separation and incompatibility of the synthesis of bioactive compounds from their biological screenings makes this process expensive and inefficient. Here, we demonstrate an on-chip platform that combines solution-based synthesis of compound libraries with high-throughput biological screenings (chemBIOS). The chemBIOS platform is compatible with both organic solvents required for the synthesis and aqueous solutions necessary for biological screenings. We use the chemBIOS platform to perform 75 parallel, three-component reactions to synthesize a library of lipidoids, followed by characterization via MALDI-MS, on-chip formation of lipoplexes, and on-chip cell screening. The entire process from the library synthesis to cell screening takes only 3 days and about 1 mL of total solutions, demonstrating the potential of the chemBIOS technology to increase efficiency and accelerate screenings and drug development.

High-throughput cell-based screening of compound libraries is utilised in drug development; however, a lack of compatible methods limits direct synthesis and testing. Here, the authors present a diverse chip based synthesis system which can be combined with cell screening and demonstrate the application.

• Prunus persica
• bud sport
• fruit shape
• genome-wide association study
• next generation sequencing

The relationship between the gene expression of Wilms tumor 1-associated protein (WTAP) and bladder cancer was investigated to study the effect of its expression on patient prognosis. Sixty-two fresh specimens of bladder transitional cell cancer tissues were collected as the bladder cancer group, while 20 normal bladder mucosa specimens comprised the control group. Hematoxylin and eosin staining was conducted to detect the pathological differences between the groups and the immunohistochemistry was used to test the expression levels of WTAP in the tissues. Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the mRNA expression levels of WTAP. Moreover, western blot analysis was used to examine the WTAP expression levels. At the same time, Cox regression multi-factor survival analysis was conducted for the related factors to the prognoses of bladder cancer patients. The structures of cells in the bladder cancer group were destroyed as was evident by the shrunken cell nuclei, while the tissues in the control group were intact. WTAP expression in the bladder cancer group was significantly increased compared with that in the control group. A small number of mRNAs and proteins were higher in the bladder cancer group than that in the control group. The differences in WTAP expression between the bladder cancer and control groups were statistically significant (P<0.05). There were obvious differences in the postoperative recurrence risk between the patients with a negative WTAP protein expression and those with a positive one (P<0.05). In conclusion, WTAP may play an important role in the occurrence and development of bladder cancer and can be considered as a potential target for bladder cancer treatment, providing a new basis for clinical diagnoses.

• WTAP
• bladder cancer
• relationship with prognosis

• differentially expressed genes
• enchondromas
• microarray
• pathways
• protein–protein interaction

• MPNST
• PNET
• TALEN
• medulloblastoma
• somatic inactivation

• Array comparative genomic hybridization
• FFPE
• melanoma

Long-term prognostic significance of loss of heterozygosity on chromosome 9p21 for localized renal cell carcinoma following surgery remains unreported. The study assessed the frequency of deletions of different loci of chromosome 9p along with immunohistochemical profile of proteins in surgically resected renal cancer tissue and correlated this with long-term outcomes.

DNA was extracted from renal tumours and corresponding normal kidney tissues in prospectively collected samples of 108 patients who underwent surgical resection for clinically localized disease between January 2001 and December 2005, providing a minimum of 9 years follow-up for each participant. After checking quality of DNA, amplified by PCR, loss of heterozygosity (LOH) on chromosome 9p was assessed using 6 microsatellite markers in 77 clear cell carcinoma. Only 5 of the markers showed LOH (D9S1814, D9S916, D9S974, D9S942, and D9S171). Protein expression of p15(INK4b), p16(INK4a), p14(ARF), CAIX, and adipose related protein (ADFP) were demonstrated by immunostaining in normal and cancer tissues. Loss of heterozygosity for microsatellite analysis was correlated with tumour characteristics, recurrence free, cancer specific, and overall survival, including significance of immunohistochemical profile of protein expressions.

The main deletion was found at loci telomeric to CDKN2A region at D9S916. There was a significant correlation between frequency of LOH stage (p = 0.005) and metastases (p = 0.006) suggesting a higher LOH for advanced and aggressive renal cell carcinoma. Most commonly observed LOH in the 3 markers: D9S916, D9S974, and D9S942 were associated with poor survival, and were statistically significant on multivariate analysis. Immunohistochemical expression of p14, p15, and p16 proteins were either low or absent in cancer tissue compared to normal.

Loss of heterozygosity of p921 chromosome is associated with aggressive tumours, and predicts cancer specific or recurrence free survival on long-term follow-up.

The online version of this article (doi:10.1186/s12885-016-2514-8) contains supplementary material, which is available to authorized users.

• Chromosome 9p
• Genetics
• Kidney cancer
• Microsatellite analysis

Cytogenetic analysis is essential for the diagnosis and prognosis of hematopoietic neoplasms in current clinical practice. Many hematopoietic malignancies are characterized by structural chromosomal abnormalities such as specific translocations, inversions, deletions and/or numerical abnormalities that can be identified by karyotype analysis or fluorescence in situ hybridization (FISH) studies. Single nucleotide polymorphism (SNP) arrays offer high-resolution identification of copy number variants (CNVs) and acquired copy-neutral loss of heterozygosity (LOH)/uniparental disomy (UPD) that are usually not identifiable by conventional cytogenetic analysis and FISH studies. As a result, SNP arrays have been increasingly applied to hematopoietic neoplasms to search for clinically-significant genetic abnormalities. A large numbers of CNVs and UPDs have been identified in a variety of hematopoietic neoplasms. CNVs detected by SNP array in some hematopoietic neoplasms are of prognostic significance. A few specific genes in the affected regions have been implicated in the pathogenesis and may be the targets for specific therapeutic agents in the future. In this review, we summarize the current findings of application of SNP arrays in a variety of hematopoietic malignancies with an emphasis on the clinically significant genetic variants.

• SNP array
• hematopoietic
• leukemia
• lymphoma
• myelodysplastic syndrome

• 1p 19q deletion
• analytical performance
• clinical performance
• oligodendroglial tumors

DNA microarray technologies have advanced rapidly and had a profound impact on examining gene expression on a genomic scale in research. This review discusses the history and development of microarray and DNA chip devices, and specific microarrays are described along with their methods and applications. In particular, microarrays have detected many novel cancer-related genes by comparing cancer tissues and non-cancerous tissues in oncological research. Recently, new methods have been in development, such as the double-combination array and triple-combination array, which allow more effective analysis of gene expression and epigenetic changes. Analysis of gene expression alterations in precancerous regions compared with normal regions and array analysis in drug-resistance cancer tissues are also successfully performed. Compared with next-generation sequencing, a similar method of genome analysis, several important differences distinguish these techniques and their applications. Development of novel microarray technologies is expected to contribute to further cancer research.

• combination array
• gene expression
• microarray

• Bioinformatics
• Computational analysis
• Genomics
• NGS software tools
• Next generation sequencing/NGS

• AKT
• cetuximab
• head and neck
• single nucleotide polymorphism (SNP)
• squamous cell carcinoma

• cancer
• allele-specific copy number analysis
• whole-genome sequencing
• aneuploidy
• tumor heterogeneity
• chromothripsis

• Alleles
• Cell Line, Tumor
• Computational Biology/methods
• DNA Copy Number Variations/genetics
• Female
• Genome, Human/genetics
• Humans
• Neoplasm Metastasis
• Neoplasms/genetics
• Neoplasms/pathology
• Reproducibility of Results
• Sequence Analysis, DNA
• Software

Microarray is one of the most recent advances being used for cancer research; it provides assistance in pharmacological approach to treat various diseases including oral lesions. Microarray helps in analyzing large amount of samples which have either been recorded previously or new samples; it even helps to test the incidence of a particular marker in tumors. Till recently, microarray's usage in dentistry has been very limited, but in future, as the technology becomes affordable, there may be increase in its usage. Here, we discuss the various techniques and applications of microarray or DNA chip.

• Cancer
• human genome
• microarray
• tissue microarray

• Genetic Predisposition to Disease
• Humans
• Myeloproliferative Disorders/etiology
• Polymorphism, Single Nucleotide/genetics
• Prognosis
• Uniparental Disomy/genetics

• Alleles
• Aneuploidy
• Biotechnology/methods
• Cell Line, Tumor
• Cell Separation
• Cyclin-Dependent Kinases/genetics
• DNA/genetics
• DNA Mutational Analysis/methods
• Disease Progression
• Female
• Flow Cytometry
• Gene Dosage
• Genetic Techniques
• Genome, Human
• Homozygote
• Humans
• Male
• Neoplasms/genetics
• Neurofibromin 1/genetics
• Ovarian Neoplasms/genetics
• Ploidies
• Point Mutation
• Tumor Suppressor Protein p53/genetics

• K08CA122833 NCI NIH HHS
• U54 HG003067 NHGRI NIH HHS
• U24 CA143845 NCI NIH HHS
• T32 HG002295 NHGRI NIH HHS
• 5R01 GM083299-14 NIGMS NIH HHS
• F32CA113126 NCI NIH HHS
• R01 GM083299 NIGMS NIH HHS
• U24CA143845 NCI NIH HHS
• U24 CA143867 NCI NIH HHS
• U24 CA143882 NCI NIH HHS
• U54 CA143798 NCI NIH HHS
• K08 CA122833 NCI NIH HHS
• U24CA143867 NCI NIH HHS
• F32 CA113126 NCI NIH HHS
• 5 T32 GM008313 NIGMS NIH HHS
• U24CA126546 NCI NIH HHS
• T32 GM008313 NIGMS NIH HHS
• U54CA143798 NCI NIH HHS
• U24 CA126546 NCI NIH HHS

In diploid eukaryotes, repair of double-stranded DNA breaks by homologous recombination often leads to loss of heterozygosity (LOH). Most previous studies of mitotic recombination in Saccharomyces cerevisiae have focused on a single chromosome or a single region of one chromosome at which LOH events can be selected. In this study, we used two techniques (single-nucleotide polymorphism microarrays and high-throughput DNA sequencing) to examine genome-wide LOH in a diploid yeast strain at a resolution averaging 1 kb. We examined both selected LOH events on chromosome V and unselected events throughout the genome in untreated cells and in cells treated with either γ-radiation or ultraviolet (UV) radiation. Our analysis shows the following: (1) spontaneous and damage-induced mitotic gene conversion tracts are more than three times larger than meiotic conversion tracts, and conversion tracts associated with crossovers are usually longer and more complex than those unassociated with crossovers; (2) most of the crossovers and conversions reflect the repair of two sister chromatids broken at the same position; and (3) both UV and γ-radiation efficiently induce LOH at doses of radiation that cause no significant loss of viability. Using high-throughput DNA sequencing, we also detected new mutations induced by γ-rays and UV. To our knowledge, our study represents the first high-resolution genome-wide analysis of DNA damage-induced LOH events performed in any eukaryote.

• Biomarkers, Tumor/genetics
• Cell Line, Tumor
• Databases, Genetic
• False Positive Reactions
• Genes, Tumor Suppressor
• Genome, Human/genetics
• Humans
• Likelihood Functions
• Linkage Disequilibrium/genetics
• Loss of Heterozygosity/genetics
• Neoplasms/enzymology
• Neoplasms/genetics
• Receptor-Like Protein Tyrosine Phosphatases, Class 2/genetics

• Wellcome Trust
• CA131341 NCI NIH HHS

The focus of this review is software for the genotyping of microarray single nucleotide polymorphisms, in particular software for Affymetrix and Illumina arrays. Different statistical principles and ideas have been applied to the construction of genotyping algorithms -- for example, likelihood versus Bayesian modelling, and whether to genotype one or all arrays at a time. The release of new arrays is generally followed by new, or updated, algorithms.

• uterine leiomyoma
• single nucleotide polymorphism array
• loh
• copy number amplification

• Chromosomes, Human, Pair 16
• Chromosomes, Human, Pair 3
• Chromosomes, Human, Pair 7
• DNA Copy Number Variations
• Female
• Gene Amplification
• Gene Dosage
• Genomics
• Humans
• Leiomyoma/genetics
• Leiomyoma/pathology
• Loss of Heterozygosity
• Oligonucleotide Array Sequence Analysis
• Polymorphism, Single Nucleotide
• Uterine Neoplasms/genetics
• Uterine Neoplasms/pathology

• ZIA ES049033 Intramural NIH HHS

• SNP array
• cancer
• copy number change
• genome-wide analysis
• genotyping

Classical tumor suppressor gene discovery has largely involved linkage analysis and loss-of-heterozygosity (LOH) screens, followed by detailed mapping of relatively large chromosomal regions. Subsequent efforts made use of genome-wide PCR-based methods to detect rare homozygous deletions. More recently, high-resolution genomic arrays have been applied to cancer gene discovery. However, accurate characterization of regions of genomic loss is particularly challenging due to sample heterogeneity, the small size of deleted regions and the high frequency of germline copy number polymorphisms. Here, we review the application of genome-wide copy number analysis to the specific problem of identifying tumor suppressor genes.

• Array CGH
• cancer
• copy number analysis
• tumor suppressor genes.