Integrative genomic analyses of recepteur d’origine nantais and its prognostic value in cancer

Abstract

Abstract. Recepteur d'origine nantais (RON) is a receptor tyrosine kinase (RTK) normally expressed at low levels in epithelial cells. RON is a 180-kDa heterodimeric protein composed of a 40-kDa α-chain and a 150-kDa transmembrane β-chain with intrinsic tyrosine kinase activity. The extracellular sequences of RON contain several domains including an N-terminal semaphorin (sema) domain, followed by the plexin, semaphorin, integrin (PSI) domain, and four immunoglobulin, plexin, transcription factor (IPT) domains. Here, we identified RON genes from 14 vertebrate genomes and found that RON exists in all types of vertebrates including fish, amphibians, birds and mammals. We found that the human RON gene showed predominant expression in the liver, lymph node, thymus, intestine, lung, mammary gland, bone marrow, brain, heart, placenta, bladder, cortex, cervix, skin, kidney and prostate. When searched in the PrognoScan database, human RON was also found to be expressed in bladder, blood, breast, glioma, esophageal, colorectal, head and neck, ovarian, lung and skin cancer. The relationship between the expression of RON and prognosis was found to vary in different cancer types, even in the same cancer from different databases. This suggests that the function of RON in these tumors may be multidimensional, not just as a tumor suppressor or oncogene. Six available single-nucleotide polymorphisms (SNPs) disrupting existing exonic splicing enhancers were identified in RON. This may contribute to the generation of active RON variants by alternative splicing, which is frequently observed in primary tumors.

Integrative genomic analyses of the RNA-binding protein, RNPC1, and its potential role in cancer prediction

“…The RNPC1 gene and amino acid sequences were selected from the Ensembl database (http://www.ensembl.org/index.html), based on orthologous and paralogous associations. The selected RNPC1 sequences were applied as queries in order to search for the RNPC1 gene using the BLAST tool at the National Center for Biotechnology Information (NCBI), in order to confirm whether their best hit was an RNPC1 gene (27)(28)(29)(30)(31)(32)(33). The number, length and structure of the exons and introns in the RNPC1 gene in all species were collected from Ensembl.…”

“…The number and length of the RNPC1 exons and introns in all sequences were then subjected to exon-intron conservation analyses. Conserved transcription factor-binding sites within the promoter region of the human RNPC1 gene were obtained from the SABiosciences' proprietary database, which combines Text Mining Application and data from the UCSC Genome Browser (http://genome.ucsc.edu/) (27)(28)(29)(30)(31)(32)(33).…”

Current and future targeted therapies for non-small-cell lung cancers with aberrant EGF receptors

“…The pretreatment detection of responsive predictor markers and individualized effective treatments will help to maximize the therapeutic index of lung cancer treatment. The last decade has seen advances in screening procedures using next-generation sequencing [85,86], large databases of genomics and proteomics for tumor types [87], and molecular markers and biochemical knowledge of the molecular basis of the development of resistance in terms of mutation. All of these will help physicians and scientists decide how a particular subset of NSCLC can be treated.…”

Integrative genomic analyses of the histamine H1 receptor and its role in cancer prediction

“…The expression profiles for normal human tissues were obtained from GeneAnnot (26) and ArrayExpress (27). Northern analysis of NCBI's uniGene dataset was also extracted (21). Moreover, protein expression of HRH1 was obtained from SPIRE (28) and MOPED (29).…”

“…Functional relevant SNPs (single nucleotide polymorphisms) of the human HRH1 gene were identified as previously described (13)(14)(15)21). The SNPs were extracted from Ensembl (http://www.ensembl.org) and NCBI's SNPdb (http://www.…”