Mutation rate of MAP2K4/MKK4 in breast carcinoma.


:The stress-activated protein kinase (SAPK) pathways represent phosphorylation cascades that convey pro-apoptotic signals. The relevant inputs include Ras proteins as well as exposure of cells to ultraviolet light, tumor-necrosis factor, and other stress-related inputs. The mitogen-activated protein kinase kinase (MAPKK) homolog MAP2K4 (MKK4, SEK, JNKK1) is a centrally-placed mediator of the SAPK pathways. MAP2K4 mutations or homozygous deletions are reported in about 5% of a wide variety of tumor types. The exception is breast cancer, where genetic inactivation in 3 of 22 (15%) cell lines had suggested that the mutational involvement of MAP2K4 might be accentuated in this tumor type. This finding might have represented an important difference, or solely a chance numerical variation. To address this question, we studied an independent panel of 20 breast cancer cell lines and xenografts for MAP2K4 alterations. We found a splice acceptor mutation accompanied by loss of the other allele in the cell line MPE600. This was the sole alteration in this panel (5% of tumors). These data seem to re-establish a rather consistent rate of genetic inactivation of MAP2K4 among most tumor types, including breast cancer. The genetic evaluation of other mediators of the SAPK pathways might offer insight into a promising, but as yet poorly defined, tumor-suppressive system.


Hum Mutat


Human mutation


Su GH,Song JJ,Repasky EA,Schutte M,Kern SE





Has Abstract


2002-01-01 00:00:00














  • Allele-specific methylated multiplex real-time quantitative PCR (ASMM RTQ-PCR), a powerful method for diagnosing loss of imprinting of the 11p15 region in Russell Silver and Beckwith Wiedemann syndromes.

    abstract::Many human syndromes involve a loss of imprinting (LOI) due to a loss (LOM) or a gain of DNA methylation (GOM). Most LOI occur as mosaics and can therefore be difficult to detect with conventional methods. The human imprinted 11p15 region is crucial for the control of fetal growth, and LOI at this locus is associated ...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Azzi S,Steunou V,Rousseau A,Rossignol S,Thibaud N,Danton F,Le Jule M,Gicquel C,Le Bouc Y,Netchine I

    更新日期:2011-02-01 00:00:00

  • Ribo-polymerase chain reaction--a facile method for the preparation of chimeric RNA/DNA applied to DNA sequencing.

    abstract::We describe ribo-polymerase chain reaction (PCR), a method for the preparation of chimeric RNA/DNA. The RNA/DNA chimeric nucleic acids are generated directly from genomic DNA starting templates with two locus-specific primers, three nucleotides in their deoxy form and the fourth in its ribo form, a DNA polymerase capa...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Mauger F,Bauer K,Semhoun J,Myers TW,Gelfand DH,Gut IG

    更新日期:2012-06-01 00:00:00

  • Somatic MED12 Nonsense Mutation Escapes mRNA Decay and Reveals a Motif Required for Nuclear Entry.

    abstract::MED12 is a key component of the transcription-regulating Mediator complex. Specific missense and in-frame insertion/deletion mutations in exons 1 and 2 have been identified in uterine leiomyomas, breast tumors, and chronic lymphocytic leukemia. Here, we characterize the first MED12 5' end nonsense mutation (c.97G>T, p...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Heikkinen T,Kämpjärvi K,Keskitalo S,von Nandelstadh P,Liu X,Rantanen V,Pitkänen E,Kinnunen M,Kuusanmäki H,Kontro M,Turunen M,Mäkinen N,Taipale J,Heckman C,Lehti K,Mustjoki S,Varjosalo M,Vahteristo P

    更新日期:2017-03-01 00:00:00

  • Novel CASK mutations in cases with syndromic microcephaly.

    abstract::Mutations in CASK cause a wide spectrum of phenotypes in humans ranging from mild X-linked intellectual disability to a severe microcephaly (MC) and pontocerebellar hypoplasia syndrome. Nevertheless, predicting pathogenicity and phenotypic consequences of novel CASK mutations through the exclusive consideration of gen...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Cristofoli F,Devriendt K,Davis EE,Van Esch H,Vermeesch JR

    更新日期:2018-07-01 00:00:00

  • Identification of seven novel germline mutations in the human E-cadherin (CDH1) gene.

    abstract::Hereditary diffuse gastric cancer (HDGC) is a cancer predisposition syndrome caused by germline mutation of the gene encoding the tumour-suppressor E-cadherin (CDH1). We describe the search for CDH1 mutations in 36 new diffuse gastric cancer families. All 16 CDH1 exons, neighbouring intronic sequence and an essential ...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: More H,Humar B,Weber W,Ward R,Christian A,Lintott C,Graziano F,Ruzzo AM,Acosta E,Boman B,Harlan M,Ferreira P,Seruca R,Suriano G,Guilford P

    更新日期:2007-02-01 00:00:00

  • Allele-specific competitive blocker PCR: a one-step method with applicability to pool screening.

    abstract::We have developed a novel one-step pool screening PCR procedure which is based on the principles of amplification refractory mutation system (ARMS) and competitive oligonuleotide priming (COP) PCR. In addition to the usual primers, this approach uses two allele-specific competitive oligonucleotides, one of which is 3'...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Orou A,Fechner B,Utermann G,Menzel HJ

    更新日期:1995-01-01 00:00:00

  • A frequent somatic mutation in CD274 3'-UTR leads to protein over-expression in gastric cancer by disrupting miR-570 binding.

    abstract::Inhibitory costimulatory molecule CD274 expresses in various cancers and contributes to cancer immune evasion by inhibiting T cell activation and proliferation, yet the regulatory mechanisms for CD274 overexpression in cancers are poorly understood. In this study, we discovered a novel mechanism of CD274 expression re...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Wang W,Sun J,Li F,Li R,Gu Y,Liu C,Yang P,Zhu M,Chen L,Tian W,Zhou H,Mao Y,Zhang L,Jiang J,Wu C,Hua D,Chen W,Lu B,Ju J,Zhang X

    更新日期:2012-03-01 00:00:00

  • Multiple osteochondromas: mutation update and description of the multiple osteochondromas mutation database (MOdb).

    abstract::Multiple osteochondromas (MO) is an autosomal dominant skeletal disease characterized by the formation of multiple cartilage-capped bone tumors growing outward from the metaphyses of long tubular bones. MO is genetically heterogeneous, and is associated with mutations in Exostosin-1 (EXT1) or Exostosin-2 (EXT2), both ...

    journal_title:Human mutation

    pub_type: 杂志文章,评审


    authors: Jennes I,Pedrini E,Zuntini M,Mordenti M,Balkassmi S,Asteggiano CG,Casey B,Bakker B,Sangiorgi L,Wuyts W

    更新日期:2009-12-01 00:00:00

  • Functional Analysis of Missense Variants in the Putative Breast Cancer Susceptibility Gene XRCC2.

    abstract::XRCC2 genetic variants have been associated with breast cancer susceptibility. However, association studies have been complicated because XRCC2 variants are extremely rare and consist mainly of amino acid substitutions whose grouping is sensitive to misclassification by the predictive algorithms. We therefore function...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Hilbers FS,Luijsterburg MS,Wiegant WW,Meijers CM,Völker-Albert M,Boonen RA,van Asperen CJ,Devilee P,van Attikum H

    更新日期:2016-09-01 00:00:00

  • Stability related bias in residues replacing glycines within the collagen triple helix (Gly-Xaa-Yaa) in inherited connective tissue disorders.

    abstract::A missense mutation leading to the replacement of one Gly in the (Gly-Xaa-Yaa)n repeat of the collagen triple helix can cause a range of heritable connective tissue disorders that depend on the gene in which the mutation occurs. Osteogenesis imperfecta results from mutations in type I collagen, Ehlers-Danlos syndrome ...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Persikov AV,Pillitteri RJ,Amin P,Schwarze U,Byers PH,Brodsky B

    更新日期:2004-10-01 00:00:00

  • An online locus-specific mutation database for familial hypertrophic cardiomyopathy.

    abstract::The aim of this locus-specific mutation database was to provide an online resource that contains summarised and updated information on familial hypertrophic cardiomyopathy (FHC)-associated mutations and related data, for researchers and clinicians. It also serves as a means of publishing previously unpublished data, w...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Fung DC,Yu B,Littlejohn T,Trent RJ

    更新日期:1999-01-01 00:00:00

  • Mutations of the human BTK gene coding for bruton tyrosine kinase in X-linked agammaglobulinemia.

    abstract::X-linked agammaglobulinemia (XLA) is an immunodeficiency caused by mutations in the gene coding for Bruton agammaglobulinemia tyrosine kinase (BTK). A database (BTKbase) of BTK mutations lists 544 mutation entries from 471 unrelated families showing 341 unique molecular events. In addition to mutations, a number of va...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Vihinen M,Kwan SP,Lester T,Ochs HD,Resnick I,Väliaho J,Conley ME,Smith CI

    更新日期:1999-01-01 00:00:00

  • Comprehensive clinical and molecular assessment of 32 probands with congenital contractural arachnodactyly: report of 14 novel mutations and review of the literature.

    abstract::Beals-Hecht syndrome or congenital contractural arachnodactyly (CCA) is a rare, autosomal dominant connective tissue disorder characterized by crumpled ears, arachnodactyly, contractures, and scoliosis. Recent reports also mention aortic root dilatation, a finding previously thought to differentiate the condition from...

    journal_title:Human mutation

    pub_type: 杂志文章,评审


    authors: Callewaert BL,Loeys BL,Ficcadenti A,Vermeer S,Landgren M,Kroes HY,Yaron Y,Pope M,Foulds N,Boute O,Galán F,Kingston H,Van der Aa N,Salcedo I,Swinkels ME,Wallgren-Pettersson C,Gabrielli O,De Backer J,Coucke PJ,De Paep

    更新日期:2009-03-01 00:00:00

  • Harmonized microarray/mutation scanning analysis of TP53 mutations in undissected colorectal tumors.

    abstract::Both the mutational status and the specific mutation of TP53 (p53) have been shown to impact both tumor prognosis and response to therapies. Molecular profiling of solid tumors is confounded by infiltrating wild-type cells, since normal DNA can interfere with detection of mutant sequences. Our objective was to identif...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Favis R,Huang J,Gerry NP,Culliford A,Paty P,Soussi T,Barany F

    更新日期:2004-07-01 00:00:00

  • Identification of novel truncated androgen receptor (AR) mutants including unreported pre-mRNA splicing variants in the 22Rv1 hormone-refractory prostate cancer (PCa) cell line.

    abstract::Advanced prostate cancer (PCa) has emerged as a public health concern due to population aging. Although androgen deprivation has proven efficacy in this condition, most advanced PCa patients will have to face failure of androgen deprivation as a treatment. Mutations in the androgen receptor (AR) from tumor cells have ...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Marcias G,Erdmann E,Lapouge G,Siebert C,Barthélémy P,Duclos B,Bergerat JP,Céraline J,Kurtz JE

    更新日期:2010-01-01 00:00:00

  • Molecular basis of hypoxanthine-guanine phosphoribosyltransferase deficiency in thirteen Spanish families.

    abstract::We have determined the molecular basis of hypoxanthine-guanine phosphoribosyltransferase (HPRT; HPRT1) deficiency in eight Lesch-Nyhan patients and in five partially HPRT deficient patients with mild to severe neurologic symptoms. Eight of these thirteen mutations have not been previously described. HPRT Zaragoza II (...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Torres RJ,Mateos FA,Molano J,Gathoff BS,O'Neill JP,Gundel RM,Trombley L,Puig JG

    更新日期:2000-04-01 00:00:00

  • Functional characterization of novel mutations in GNPAT and AGPS, causing rhizomelic chondrodysplasia punctata (RCDP) types 2 and 3.

    abstract::Rhizomelic chondrodysplasia punctata (RCDP) is a disorder of peroxisome metabolism resulting from a deficiency of plasmalogens, a specialized class of membrane phospholipids. Classically, patients have a skeletal dysplasia and profound mental retardation, although milder phenotypes are increasingly being identified. I...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Itzkovitz B,Jiralerspong S,Nimmo G,Loscalzo M,Horovitz DD,Snowden A,Moser A,Steinberg S,Braverman N

    更新日期:2012-01-01 00:00:00

  • Molecular diagnosis of inherited disorders: lessons from hemoglobinopathies.

    abstract::Hemoglobinopathies constitute a major health problem worldwide, with a high carrier frequency, particularly in certain regions where malaria has been endemic. These disorders are characterized by a vast clinical and hematological phenotypic heterogeneity. Over 1,200 different genetic alterations that affect the DNA se...

    journal_title:Human mutation

    pub_type: 杂志文章,评审


    authors: Patrinos GP,Kollia P,Papadakis MN

    更新日期:2005-11-01 00:00:00

  • Highly sensitive mutation screening by REF with low concentrations of urea: A blinded analysis of a 2-kb region of the p53 gene reveals two common haplotypes.

    abstract::Restriction endonuclease fingerprinting (REF), a hybrid modification of single-strand conformation polymorphism (SSCP) and restriction endonuclease digestion, has been used previously to detect mutations in 1- to 2-kb segments of DNA. This paper demonstrates that fragment resolution, and thus sensitivity of REF, can b...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Feng J,Buzin CH,Tang SH,Scaringe WA,Sommer SS

    更新日期:1999-01-01 00:00:00

  • EYS is a major gene for rod-cone dystrophies in France.

    abstract::Autosomal-recessive retinitis pigmentosa (arRP) was recently associated with mutations in a novel gene EYS, spanning over 2 Mb, making it the largest known gene expressed in the human eye. The purpose of this study was to establish the prevalence and nature of EYS mutations in a clinically well-characterized cohort of...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Audo I,Sahel JA,Mohand-Saïd S,Lancelot ME,Antonio A,Moskova-Doumanova V,Nandrot EF,Doumanov J,Barragan I,Antinolo G,Bhattacharya SS,Zeitz C

    更新日期:2010-05-01 00:00:00

  • Detecting false-positive signals in exome sequencing.

    abstract::Disease gene discovery has been transformed by affordable sequencing of exomes and genomes. Identification of disease-causing mutations requires sifting through a large number of sequence variants. A subset of the variants are unlikely to be good candidates for disease causation based on one or more of the following c...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Fuentes Fajardo KV,Adams D,NISC Comparative Sequencing Program.,Mason CE,Sincan M,Tifft C,Toro C,Boerkoel CF,Gahl W,Markello T

    更新日期:2012-04-01 00:00:00

  • Molecular basis of congenital erythropoietic porphyria: mutations in the human uroporphyrinogen III synthase gene.

    abstract::Congenital erythropoietic porphyria (CEP) is an autosomal recessive inborn error of metabolism that results from the markedly deficient activity of the fourth enzyme in the heme biosynthetic pathway, uroporphyrinogen III synthase (URO-synthase). To date, 17 mutations have been described including 11 missense, one nons...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Xu W,Astrin KH,Desnick RJ

    更新日期:1996-01-01 00:00:00

  • Mutations and polymorphisms in the human N-acetylglutamate synthase (NAGS) gene.

    abstract::N-acetylglutamate synthase (NAGS) deficiency, an autosomal recessive disorder, is the last urea cycle disorder for which molecular testing became available. This is the first comprehensive report of 21 mutations that cause NAGS deficiency and of commonly found polymorphisms in the NAGS gene. Five mutations are reporte...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Caldovic L,Morizono H,Tuchman M

    更新日期:2007-08-01 00:00:00

  • Postzygotic single-nucleotide mosaicisms contribute to the etiology of autism spectrum disorder and autistic traits and the origin of mutations.

    abstract::The roles and characteristics of postzygotic single-nucleotide mosaicisms (pSNMs) in autism spectrum disorders (ASDs) remain unclear. In this study of the whole exomes of 2,361 families in the Simons Simplex Collection, we identified 1,248 putative pSNMs in children and 285 de novo SNPs in children with detectable par...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Dou Y,Yang X,Li Z,Wang S,Zhang Z,Ye AY,Yan L,Yang C,Wu Q,Li J,Zhao B,Huang AY,Wei L

    更新日期:2017-08-01 00:00:00

  • RRBS-analyser: a comprehensive web server for reduced representation bisulfite sequencing data analysis.

    abstract::In reduced representation bisulfite sequencing (RRBS), genomic DNA is digested with the restriction enzyme and then subjected to next-generation sequencing, which enables detection and quantification of DNA methylation at whole-genome scale with low cost. However, the data processing, interpretation, and analysis of t...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Wang T,Liu Q,Li X,Wang X,Li J,Zhu X,Sun ZS,Wu J

    更新日期:2013-12-01 00:00:00

  • A collection of 33 novel human mtDNA homoplasmic variants.

    abstract::Mitochondria are involved in cellular energy production via oxidative phosphorylation and this function may be damaged by any mutation in mitochondrial DNA (mtDNA). To identify novel mtDNA mutations, we have developed a program to systematically screen the entire mitochondrial genome in a large number of individuals w...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Crimi M,Sciacco M,Galbiati S,Bordoni A,Malferrari G,Del Bo R,Biunno I,Bresolin N,Comi GP

    更新日期:2002-11-01 00:00:00

  • Detection of heterozygous deletions and duplications in the MECP2 gene in Rett syndrome by Robust Dosage PCR (RD-PCR).

    abstract::Fifty to eighty percent of Rett syndrome (RTT) cases have point mutations in the gene encoding methyl-CpG-binding protein-2 (MECP2). A fraction of MECP2 negative classical RTT patients has large heterozygous deletions. Robust Dosage PCR (RD-PCR) assays were developed as a rapid, convenient and accurate method to detec...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Shi J,Shibayama A,Liu Q,Nguyen VQ,Feng J,Santos M,Temudo T,Maciel P,Sommer SS

    更新日期:2005-05-01 00:00:00

  • Identification of a novel NOG gene mutation (P35S) in an Italian family with symphalangism.

    abstract::Symphalangism (SYM or SYM1) is an autosomal dominant disorder characterized by multiple joint fusions. The disease is caused by mutations of the NOG gene, that maps to chromosome 17q22. So far, only six independent NOG mutations have been identified. We have analysed an Italian family in which father and son had bilat...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Mangino M,Flex E,Digilio MC,Giannotti A,Dallapiccola B

    更新日期:2002-03-01 00:00:00

  • Broad phenotypic variability in a single pedigree with a novel 1410delC mutation in the PST domain of the PAX6 gene.

    abstract::The PAX6 mutation present in an individual with aniridia was determined and phenotypic features of immediate relatives carrying the same mutation investigated. Mutation analysis revealed a novel single base deletion 1410delC in the PAX6 gene in ten affected individuals. Clinical features ranged from total aniridia to ...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Sale MM,Craig JE,Charlesworth JC,FitzGerald LM,Hanson IM,Dickinson JL,Matthews SJ,Heyningen Vv Vv,Fingert JH,Mackey DA

    更新日期:2002-10-01 00:00:00

  • ADIPOR1 Is Mutated in Syndromic Retinitis Pigmentosa.

    abstract::Retinitis pigmentosa (RP) is a genetically heterogeneous retinal disorder. Despite the numerous genes associated with RP already identified, the genetic basis remains unknown in a substantial number of patients and families. In this study, we performed whole-exome sequencing to investigate the molecular basis of a syn...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Xu M,Eblimit A,Wang J,Li J,Wang F,Zhao L,Wang X,Xiao N,Li Y,Wong LJ,Lewis RA,Chen R

    更新日期:2016-03-01 00:00:00