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KIT Gene (kit + gene)
Selected AbstractsCutaneous T-cell lymphoma-associated lung cancers show chromosomal aberrations differing from primary lung cancerGENES, CHROMOSOMES AND CANCER, Issue 2 2008Sonja Hahtola Cutaneous T-cell lymphoma (CTCL) patients have an increased risk of certain secondary cancers, the most common of which are lung cancers, especially small cell lung cancer. To reveal the molecular pathogenesis underlying CTCL-associated lung cancer, we analyzed genomic aberrations in CTCL-associated and reference lung cancer samples. DNA derived from microdissected lung cancer cells of five CTCL-associated lung cancers and five reference lung cancers without CTCL association was analyzed by comparative genomic hybridization (CGH). Fluorescent in situ hybridization (FISH), immunohistochemistry (IHC), and loss of heterozygosity (LOH) analysis were performed for selected genes. In CTCL-associated lung cancer, CGH revealed chromosomal aberrations characterizing both lung cancer and CTCL, but also losses of 1p, and 19, and gains of 4q and 7, hallmarks of CTCL. LOH for the CTCL-associated NAV3 gene was detected in two of the four informative primary lung cancers. FISH revealed increased copy number of the KIT gene in 3/4 of CTCL-associated lung cancers and 1/5 of primary lung cancers. PDGFRA and VEGFR2 copy numbers were also increased. IHC showed moderate KIT expression when the gene copy number was increased. CTCL-associated lung cancer shows chromosomal aberrations different from primary lung cancer, especially amplifications of 4q, a chromosome arm frequently deleted in the latter tumor type. Copy numbers and expression of selected genes in chromosome 4 differed between CTCL-associated and reference lung cancers. These preliminary observations warrant further prospective studies to identify the common underlying factors between CTCL and CTCL-associated lung cancer. This article contains Supplementary Material available at http://www.interscience.wiley.com/jpages/1045-2257/suppmat. © 2007 Wiley-Liss, Inc. [source] Aberrant expression of glycosylation in juvenile gastrointestinal stromal tumorsPROTEOMICS - CLINICAL APPLICATIONS, Issue 9 2008Tsuyoshi Takahashi Abstract Most adult gastrointestinal stromal tumors (GIST) are thought to be caused by activating mutations in the KIT or PDGFRA gene. However, many juvenile GIST lack either mutation and are considered to develop with a different pathogenesis. To investigate the molecular characteristics of juvenile GIST, we analyzed the proteome difference in phosphorylated protein between adult and juvenile GIST. Eleven GIST samples (seven adult cases and four juvenile cases lacking either mutation) were analyzed by using immunostaining and LC-MS/MS. Comparative analysis of tyrosine-phosphorylated protein levels showed that juvenile GIST possessed phosphorylated KIT in spite of lacking mutation in the KIT gene. Moreover, downstream signals of KIT were also activated as in adult GIST. Although, SDS-PAGE gels showed that there was a difference of each KIT bands between adult and juvenile GIST, they became the same after removal of N-glycans or sialic acids. Moreover, one of the most typical enzymes, ST6Gal1, which transfers Neu5Ac residues in ,2-6 linkage to Gal ,1-4GlcNAc units on N-glycans, is significantly less expressed in juvenile GIST. This suggests that the difference in KIT is generated by post-translational modification and may play a role in the progression of juvenile GIST. [source] Genetic heterogeneity and selection signature at the KIT gene in pigs showing different coat colours and patternsANIMAL GENETICS, Issue 5 2010L. Fontanesi Summary Mutations in the porcine KIT gene (Dominant white locus) have been shown to affect coat colours and colour distribution in pigs. We analysed this gene in several pig breeds and populations (Sicilian black, completely black or with white patches; Cinta Senese; grey local population; Large White; Duroc; Hampshire; Pietrain; wild boar; Meishan) with different coat colours and patterns, genotyping a few polymorphisms. The 21 exons and parts of the intronic regions were sequenced in these pigs and 69 polymorphisms were identified. The grey-roan coat colour observed in a local grey population was completely associated with a 4-bp deletion of intron 18 in a single copy KIT gene, providing evidence that this mutation characterizes the Id allele described in the early genetic literature. The white patches observed in black Sicilian pigs were not completely associated with the presence of a duplicated KIT allele (Ip), suggesting that genetic heterogeneity is a possible cause of different coat colours in this breed. Selection signature was evident at the KIT gene in two different belted pig breeds, Hampshire and Cinta Senese. The same mutation(s) may cause the belted phenotype in these breeds that originated in the 18th,19th centuries from English pigs (Hampshire) and in Tuscany (Italy) in the 14th century (Cinta Senese). Phylogenetic relationships of 28 inferred KIT haplotypes indicated two clades: one of Asian origin that included Meishan and a few Sicilian black haplotypes and another of European origin. [source] Genetic heterogeneity at the bovine KIT gene in cattle breeds carrying different putative alleles at the spotting locusANIMAL GENETICS, Issue 3 2010L. Fontanesi Summary According to classical genetic studies, piebaldism in cattle is largely influenced by the allelic series at the spotting locus (S), which includes the SH (Hereford pattern), S+ (non-spotted) and s (spotted) alleles. The S locus was mapped on bovine chromosome 6 in the region containing the KIT gene. We investigated the KIT gene, analysing its variability and haplotype distribution in cattle of three breeds (Angus, Hereford and Holstein) with different putative alleles (S+, SH and s respectively) at the S locus. Resequencing of a whole of 0.485 Mb revealed 111 polymorphisms. The global nucleotide diversity was 0.087%. Tajima's D- values were negative for all breeds, indicating putative directional selection. Of the 28 inferred haplotypes, only five were observed in the Hereford breed, in which one was the most frequent. Coalescent simulation showed that it is highly unlikely (P < 10E-6) to obtain this low number of haplotypes conditionally on the observed number of segregating SNPs. Therefore, the neutral model could be rejected for the Hereford breed, suggesting that a selection sweep occurred at the KIT locus. Twelve haplotypes were inferred in Holstein and Angus. For these two breeds, the neutral model could not be rejected. High heterogeneity of the KIT gene was confirmed from a phylogenetic analysis. Our results suggest a role of the KIT gene in determining the SH allele(s) in the Hereford, but no evidence of selective sweep was obtained in Holstein, suggesting that complex mechanisms (or other genes) might be the cause of the spotted phenotype in this breed. [source] Seven novel KIT mutations in horses with white coat colour phenotypesANIMAL GENETICS, Issue 5 2009B. Haase Summary White coat colour in horses is inherited as a monogenic autosomal dominant trait showing a variable expression of coat depigmentation. Mutations in the KIT gene have previously been shown to cause white coat colour phenotypes in pigs, mice and humans. We recently also demonstrated that four independent mutations in the equine KIT gene are responsible for the dominant white coat colour phenotype in various horse breeds. We have now analysed additional horse families segregating for white coat colour phenotypes and report seven new KIT mutations in independent Thoroughbred, Icelandic Horse, German Holstein, Quarter Horse and South German Draft Horse families. In four of the seven families, only one single white horse, presumably representing the founder for each of the four respective mutations, was available for genotyping. The newly reported mutations comprise two frameshift mutations (c.1126_1129delGAAC; c.2193delG), two missense mutations (c.856G>A; c.1789G>A) and three splice site mutations (c.338-1G>C; c.2222-1G>A; c.2684+1G>A). White phenotypes in horses show a remarkable allelic heterogeneity. In fact, a higher number of alleles are molecularly characterized at the equine KIT gene than for any other known gene in livestock species. [source] New mutations of KIT gene in two Chinese patients with piebaldismBRITISH JOURNAL OF DERMATOLOGY, Issue 6 2006Z-M. Lin No abstract is available for this article. [source] Pathology of gastrointestinal stromal tumorsPATHOLOGY INTERNATIONAL, Issue 1 2006Seiichi Hirota Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors in the gastrointestinal tract. It was found that most GIST expressed KIT, a receptor tyrosine kinase encoded by protooncogene c- kit. In normal gastrointestinal wall, KIT is expressed by interstitial cells of Cajal (ICC), which are a pacemaker for autonomous gastrointestinal movement. Because both GIST and ICC are double-positive for KIT and CD34, and because familial and multiple GIST appear to develop from diffuse hyperplasia of ICC, GIST are considered to originate from ICC or their precursor cells. It was also found that approximately 90% of the sporadic GIST have somatic gain-of-function mutations of the c- kit gene, and that the patients with familial and multiple GIST have germline gain-of-function mutations of the c- kit gene. These facts strongly suggest that the c- kit gene mutations are a cause of GIST. Approximately half of the sporadic GIST without c- kit gene mutations were demonstrated to have gain-of-function mutations in platelet-derived growth factor receptor-, (PDGFRA) gene that encodes another receptor tyrosine kinase. Because KIT is immunohistochemically negative in a minority of GIST, especially in PDGFRA gene mutation-harboring GIST, mutational analyses of c- kit and PDGFRA genes may be required to diagnose such GIST definitely. Imatinib mesylate was developed as a selective tyrosine kinase inhibitor. It inhibits constitutive activation of mutated KIT and PDGFRA, and is now being used for KIT-positive metastatic or unresectable GIST as a molecular target drug. Confirmation of KIT expression by immunohistochemistry is necessary for application of the drug. The effect of imatinib mesylate is different in various types of c- kit and PDGFRA gene mutations, and the secondary resistance against imatinib mesylate is often acquired by the second mutation of the identical genes. Mutational analyses of c- kit and PDGFRA genes are also significant for prediction of effectiveness of drugs including newly developed agents. [source] Absence of c- kit gene mutations in gastrointestinal stromal tumours from neurofibromatosis type 1 patientsTHE JOURNAL OF PATHOLOGY, Issue 1 2004Kazuo Kinoshita Abstract Most sporadic gastrointestinal stromal tumours (GISTs) have somatic c- kit gene mutations that are considered to be causal. Neurofibromatosis type 1 (NF1) is caused by mutations of the NF1 gene and NF1 patients have an increased risk of developing GISTs. Since most neoplasms are considered to develop as a result of the combination of several gene mutations, these findings suggest that GISTs from NF1 patients might have somatic c- kit gene mutations and that sporadic GISTs from non-NF1 patients might have somatic NF1 gene mutations. The present study analysed 29 GISTs from seven NF1 patients for c- kit gene mutations and ten sporadic GISTs from ten non-NF1 patients for NF1 mutations. Exons 9, 11, 13, and 17 of the c- kit gene were amplified and directly sequenced after the extraction of genomic DNA from wax-embedded tissues from 26 GISTs from five NF1 patients. The whole coding region of the c- kit cDNA and the whole coding region of the NF1 cDNA were amplified and directly sequenced after RNA extraction and cDNA synthesis in three fresh GIST tissues from two NF1 patients and ten fresh GIST tissues from ten non-NF1 patients. Of the ten sporadic GISTs, eight had heterozygous mutations at exon 11, and one at exon 9, of c- kit. Heterozygous NF1 gene mutations were detected in GISTs from the two NF1 patients from whom fresh tissues were available. None of the 29 GISTs derived from NF1 patients had detectable c- kit gene mutations and none of the ten GISTs derived from non-NF1 patients had detectable NF1 mutations. These results suggest that the pathogenesis of GISTs in NF1 patients is different from that in non-NF1 patients. Copyright © 2004 John Wiley & Sons, Ltd. 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