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Genetic interactions between ANLN and KDR are prognostic for breast cancer survival.

Xiaofeng Dai | Xiao Chen | Olivier Hakizimana | Yi Mei
Oncology reports | 2019

Single nucleotide polymorphisms (SNPs) are the most common genetic variation in mammalian cells with prognostic potential. Anillin‑actin binding protein (ANLN) has been identified as being involved in PI3K/PTEN signaling, which is critical in cell life/death control, and kinase insert domain receptor (KDR) encodes a key receptor mediating the cancer angiogenesis/metastasis switch. Knowledge of the intrinsic connections between PI3K/PTEN and KDR signaling, which represent two critical transitions in carcinogenesis, led the present study to investigate the effects of the potential synergy between ANLN and KDR on breast cancer outcome and identify relevant SNPs driving such a synergy at the genetic level. The survival associations of SNPs from KDR and ANLN were assessed through pairwise interaction survival analysis, quantitative trait loci analysis, pathway enrichment analysis and network construction, and the interactions between ANLN and KDR were validated in vitro. It was found that both rare homozygotes in the ANLN:rs12535394 and KDR:rs11133360 SNP pair are prognostic of favorable breast cancer survival and underpin the prominent roles of the immune response in cancer state control. This study contributes to breast cancer prognosis and therapeutic design by providing genetic evidence of interactions between ANLN and KDR, and suggesting the prominent role of the immune response in driving the synergies between the cancer cell life/death and angiogenesis/metastasis transitions during carcinogenesis.

Pubmed ID: 31578580

Associated grants

None

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ATCC (tool)

RRID:SCR_001672

Global nonprofit biological resource center (BRC) and research organization that provides biological products, technical services and educational programs to private industry, government and academic organizations. Its mission is to acquire, authenticate, preserve, develop and distribute biological materials, information, technology, intellectual property and standards for the advancement and application of scientific knowledge. The primary purpose of ATCC is to use its resources and experience as a BRC to become the world leader in standard biological reference materials management, intellectual property resource management and translational research as applied to biomaterial development, standardization and certification. ATCC characterizes cell lines, bacteria, viruses, fungi and protozoa, as well as develops and evaluates assays and techniques for validating research resources and preserving and distributing biological materials to the public and private sector research communities.

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dbSNP (tool)

RRID:SCR_002338

Database as central repository for both single base nucleotide substitutions and short deletion and insertion polymorphisms. Distinguishes report of how to assay SNP from use of that SNP with individuals and populations. This separation simplifies some issues of data representation. However, these initial reports describing how to assay SNP will often be accompanied by SNP experiments measuring allele occurrence in individuals and populations. Community can contribute to this resource.

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RRID:SCR_003193

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GeneMANIA (tool)

RRID:SCR_005709

Data analysis service to predict the function of your favorite genes and gene sets. Indexing 1,421 association networks containing 266,984,699 interactions mapped to 155,238 genes from 7 organisms. GeneMANIA interaction networks are available for download in plain text format. GeneMANIA finds other genes that are related to a set of input genes, using a very large set of functional association data. Association data include protein and genetic interactions, pathways, co-expression, co-localization and protein domain similarity. You can use GeneMANIA to find new members of a pathway or complex, find additional genes you may have missed in your screen or find new genes with a specific function, such as protein kinases. Your question is defined by the set of genes you input. If members of your gene list make up a protein complex, GeneMANIA will return more potential members of the protein complex. If you enter a gene list, GeneMANIA will return connections between your genes, within the selected datasets. GeneMANIA suggests annotations for genes based on Gene Ontology term enrichment of highly interacting genes with the gene of interest. GeneMANIA is also a gene recommendation system. GeneMANIA is also accessible via a Cytoscape plugin, designed for power users. Platform: Online tool, Windows compatible, Mac OS X compatible, Linux compatible, Unix compatible

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PredictSNP (tool)

RRID:SCR_006327

Consensus classifier tool that combines six of the top performing tools for the prediction of the effects of mutation on protein function. The obtained results are provided together with annotations extracted from the Protein Mutant Database and the UniProt database. A stand-alone version is also available.

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RRID:SCR_006802

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RRID:SCR_012773

Integrated database resource consisting of 16 main databases, broadly categorized into systems information, genomic information, and chemical information. In particular, gene catalogs in completely sequenced genomes are linked to higher-level systemic functions of cell, organism, and ecosystem. Analysis tools are also available. KEGG may be used as reference knowledge base for biological interpretation of large-scale datasets generated by sequencing and other high-throughput experimental technologies.

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cBioPortal (tool)

RRID:SCR_014555

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RRID:SCR_015723

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RRID:CVCL_0598

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