Atlas of Genetics and Cytogenetics in Oncology and Haematology


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ASCL1 (Achaete-scute homolog 1 or achaete-scute complex homolog 1)

Identity

Other namesASH1
HASH1
MASH1
HGNC (Hugo) ASCL1
LocusID (NCBI) 429
Location 12q23.2
Location_base_pair Starts at 103351452 and ends at 103354294 bp from pter ( according to hg19-Feb_2009)  [Mapping]
Note Renault B et al performed fluorescent in situ hybridisation using YAC 896h that contains ASCL1 and other chromosome 12 specific markers such as IGF1, PAH and TRA1 to localise ASCL1. They established using genetic markers that ASCL1 localises distal to Phenylalanine hydroxylase (PAH) and proximal to tumor rejection antigen (TRA1) on chromosome 12q22-q23 cytogenic interval. (Beatrice Renault et al. Genomics 30, 81-83 (1995))
LINEAGE: Eukaryota, Metazoa, Chordata, Craniata, Vertebrata, Euteleostomi, Mammalia, Eutheria, Euarchontoglires, Primates, Haplorrhini, Catarrhini, Hominidae, Homo. NCBI GI#: g119618109; g22658430; g20455478; g13111927; g12803079; g55743094; g306460; g13325212

DNA/RNA

 
  A: Schematic representation of the ASCL1 genomic DNA depicting exons, introns, transcript and mRNA with untranslated and coding region. B: Schematic diagram showing HASH1/ASCL1 promoter with proximal and distal repressors, HASH1/ASCL1 class C site, enhancer Sp1 binding sites and transcription initiation sites (TATA box and INR (initiator) element).
Description 2 exons spanning 2824bp although only exon1 codes for the protein. Orientation '+' strand. Exon 1 101875594-101876910 (1317 bp), Exon 2 101877270-101878417 (1148 bp), Intron 1-2 101876911-101877269 (359 bp). Gene id= 429 (KEGG). Refseq: NM_004316.2
HASH1/ASCL1 promoter has two independent transcription start sites of which proximal INR element (YYANYY consensus binding site) plays a predominant role. The general enhancer has several Sp1 binding sites. Tissue restricted expression control comes from the repressor regions present in the distal (over 13.5kb upstream) and proximal 5' flanking region. The proximal repressor is shown to have a class C element site to which HES1 can bind and regulate HASH1/ASCL1 expression.
Variant: 158--158 Glu to Gly (E to G) Var_013179 in P50553
Transcription 2.46 Kb mRNA, coding sequence 711 bp

Protein

Note This gene encodes a member of the basic helix-loop-helix (bHLH) family of transcription factors. The protein activates transcription by binding to the E box (5'-CANNTG-3'). Dimerization with other bHLH proteins is required for efficient DNA binding. This protein plays a role in the neuronal commitment and differentiation and in the generation of olfactory and autonomic neurons. It is highly expressed in medullary thyroid cancer (MTC) and small cell lung cancer (SCLC) and may be a useful marker for these cancers. The proximal coding region of the cDNA contains a striking 14-copy repeat of the triplet CAG that exhibits polymorphism in human genomic DNA The presence of a CAG repeat in the gene suggests that it could play a role in tumor formation.
Protein size: 237 aa, 25.45kDa. Refseq: NP_004307.2
 
  Schematic representation of ASCL1 protein depicting various motifs such as poly alanine and poly glutamine repeats, a basic motif and a bHLH DNA binding motif.
Description The amino terminal of the protein contains poly alanine and poly glutamine repeat rich region. The polyglutamine length polymorphism in ASCL1 has been postulated that it could influence predispositions to Parkinson's disease. The carboxy terminus of the protein contains the basic helix loop helix domain, which is important for interaction with other transcription factors.
Expression The gene product is expressed basically nuclear and is expressed in tissues like brain, lung and nervous system.
Function ASCL1 functions as a bHLH transcription factor that binds to E-box whose canonical sequence is 5'CANNTG 3'. It also acts as protein binding, transcription factor, and in cell differentiation. MASH1/ASCL1 is expressed during development of rat retina and interacts specifically with an E-box identified in the promoter for the opsin gene during rod photoreceptor differentiation. NOTCH1 and its downstream signal transducer HES1 regulates the transcription of HASH1/ASCL1 and is very instrumental in neuronal developmental pathways particularly dictating neuroendocrine differentiation in various organs.
Interacting partners: E1A binding protein p300, Ubiquilin 1, Bone morphogenetic protein 2 (BMP2), Trancription factor 3 (TF3), Transcription factor 4 (TF4), Myocyte specific Enhancer factor 2A (MSEF2A), Neurogenin.
Homology Mus musculus Ascl1 achaete-scute complex homolog-like 1 (Drosophila) NM_008553.2; Rattus norvegicus Ascl1 achaete-scute complex homolog-like 1 (Drosophila) NM_022384.1; Canis familiaris similar to achaete-scute homolog 1 LOC482628; Danio Rerio achaete scute homolog A asha NM_131219.1.

Mutations

Note Congenital central hypoventilation syndrome is a rare disorder of the chemical control of breathing. The ASCL1--PHOX2A--PHOX2B developmental cascade was proposed as a candidate pathway for this disorder, as well as for Haddad syndrome, because the cascade controls the development of neurons with a definitive or transient noradrenergic phenotype. De Pontual et al. identified heterozygosity for mutations in the ASCL1 gene in 2 patients with CCHS and 1 patient with Haddad syndrome. The authors also developed an in vitro model of noradrenergic differentiation in neuronal progenitors derived from the mouse vagal neural crest. All Ascl1 mutant alleles result in impaired noradrenergic neuronal development when over expressed from adenoviral constructs.
ALLELIC VARIANTS
1. ASCL1 C52A, PRO18THR
In a patient with CCHS, de Pontual et al identified heterozygosity for a 52C-A transversion in the ASCL1 gene, translating in a pro18-to-thr substitution. The patient was also heterozygous for a polyalanine expansion mutation in PHOX2B, which is known to induce CCHS.
2. ASCL1, 15-BP DEL, NT111
Heterozygosity for a 15-bp deletin (111-115 Del 15nt) in the ASCL1 gene was reported in a patient with CCHS by de Pontual et al. The mutation was predicted to result in loss of 5 of 13 alanine residues (ala37-ala41) in a polyalanine tract.
3. ASCL1, 24-BP DEL, NT108
Another heterozygosity for of 24-bp deletion (108-131del24nt) in the ASCL1 gene was identified in a patient with Haddad syndrome (209880), de Pontual et al The mutation was predicted to result in loss of 8 of 13 alanine residues (ala36-ala43) in a polyalanine tract.
Genetic association with Parkinson's disease has been shown by Ide M et al (PMID=16021468) and that with sudden infant death syndrome or (SIDS) has been shown by Weese-Mayer DE et al (PMID= 15240857)

Implicated in

Note Upon characterization of expression of ASCL1 in several human cancer cell lines and tumors it is found that ASCL1 is highly expressed in and has been implicated to impart neuroendocrine behaviour to various NE- tumors e.g gastrointestinal NE carcinoma (NEC), Pheochromocytomas, olfactory neuroblastomas or esthesioneuroblastoma, pulmonary and thyroid carcinoids, Medullary thyroid cancer (MTC), small cell lung cell cancer (SCLC) and recently in prostate small cell carcinoma. Apart from this, ASCL1 protein is also shown to be highly upregulated in progressive secondary glioblastoma (GBM). Notch signalling down regulates ASCL1 levels but its expression is shown to be very minimal or non-existent in neuroendocrine tumors and hence inhibition of ASCL1 expression that has been implicated to impart neuroendocrine behaviour could be a therapeutic target to suppress tumor growth.
  
Entity Neuroendocrine Tumors
Note Neuroendocrine tumors originate from cells that are capable of amine precursor (such as dopa and 5-hydroxytryptophan) uptake and decarboxylation (APUD cells). As a result, these tumors have high intracellular levels of carboxyl groups and nonspecific esterase, which are used as a neuroendocrine marker. These tumors have NE- phenotype characterized by expression of ACTH, vasopressin, calcitonin gene related peptide (CALCA/CGRP), Gastrin releasing peptide and secretory proteins like synaptophysin and chromogranins, serotonin. HASH1/ASCL1 appears to be cardinal/ hallmark feature of each of these tumor types. Clinically Chromogranin A is most commonly used as a marker to identify NE- tumors.
  
Entity Olfactory neuroblastomas or Esthesioneuroblastoma (ENB)
Note paranasal sinus nasal cavity esthesioneuroblastoma or esthesioneurocytoma, esthesioneuroma, and esthesioneuroepithelioma
Disease Esthesioneuroblastoma (ENB) is a rare tumor arising out of the nasal vault from cells of the developing sympathetic nervous system. When neuroblastoma cells are induced to differentiate, as indicated by neuronal morphology and upregulation of neuronal marker genes, the HASH-1/ASCL1 expression is rapidly downregulated with a concomitant, transient upregulation of HES-1. ENB is generally a slow-growing tumor with a high 5-year survival (81%). Recurrences usually occur within the first 2 years. However, late recurrences are common, and hence follow-up must be done for a prolonged time.
Prognosis HASH1/ASCL1 is expressed in immature olfactory neurons and is critical for their development. Mhawech et al found distinct expression of HASH1/ASCL1 in all estersioneuroblastoma samples as compared to the poorly differentiated tumors that were negative. They also report inverse correlation between grades of esthesioneuroblastoma and HASH1/ASCL1 mRNA levels and propose that HASH1/ASCL1 could be used as useful tool to distinguish estersioneuroblastoma from poorly differentiated tumors of sinonasal region.
  
Entity Pulmonary and thyroid carcinoids
Note Carcinoid tumors or carcinoids
Disease These tumors originate in hormone-producing cells of the gastrointestinal (GI) tract (i.e., esophagus, stomach, small intestine, colon), the respiratory tract (i.e., lungs, trachea, bronchi), the hepatobiliary system (i.e., pancreas, gallbladder, liver), and the reproductive glands (i.e., testes, ovaries). Carcinoids are classified as slow growing neuroendocrine tumors. They develop in peptide- and amine-producing cells, which release hormones like serotonin in response to signals from the nervous system. Excessive amounts of these hormones cause a condition called carcinoid syndrome in approximately 10% of patients with carcinoid tumors.
Prognosis Multiple endocrine neoplasia type 1 (MEN1) is a genetic disorder that increases the risk for neuroendocrine tumors, including carcinoids. Gastrointestinal conditions (e.g., peptic ulcer disease, pernicious anemia, atrophic gastritis, Zollinger-Ellison syndrome) increase the risk for carcinoid tumors of the GI tract. Carcinoid patients also have an increased risk for Cushing's syndrome. Atypical Carcinoids (fast growing and potentially metastatic) express high levels of HASH1/ASCL1 (although lower than NECs) and is associated with poor prognosis for survival.
RAF-1 activation is detrimental to tumorigenesis in carcinoid cells. Raf1 activation in an estrogen inducible system in pancreatic carcinoid cell line (BON) and in pulmonary cell lines leads to marked reduction in NE-markers such as 5-HT, chromogranin A, and synaptophysin and HASH1/ASCL1 has been observed.
  
Entity Medullary thyroid cancer (MTC)
Disease Medullary thyroid cancer is a neuroendocrine tumor derived from the parafollicular calcitonin producing C cells of thyroid and accounts for about 3% of thyroid cancers.
Inheritance: About 20% of have an inherited form of the disease and familial MTC are transmitted in an autosomal dominant fashion involving mutations in the RET proto-oncogene. So far surgery remains only curative treatment modality.
Prognosis The classical tumor marker and the secreted hormone is calcitonin which is tightly regulated by Notch signalling and HASH1/ASCL1 levels. It has also been shown that by activating RAF-1 signalling mediated by MEK induction leads to complete suppression of ASCL1 and mRNA protein which is frequently upregulated in MTC. HASH1/ASCL1 over expression is linked to poor prognostic value.
  
Entity Small cell lung cancer (SCLC)
Note Oat cell carcinoma
Disease SCLC cells are small and round to fusiform with scant cytoplasm.SCLC tumors are poorly differentiated neuroendocrine tumors as compared to bronchoid carcinoid tumors and is an aggressive and highly metastatic tumor, accounting to about 20% death from lung cancer. Owing to its NE-phenotype, these tumors secrete chromogranin A, GRP and calcitonin in addition to over expressed HASH1/ASCL1.
Genetically c-myc has shown to be over expressed by gene amplification and retinoblastoma (Rb) is frequently mutated in SCLC. P53 and PTEN also show aberrant expression. Loss of chromosome 3 sequences appears to occur frequently at the very earliest stages of neoplastic transformation. Losses at the short arms of chromosome 3 and 17 and the long arm of 5 are seen consistently in almost all SCLC patients. Although to date, there are no known examples of amplification or rearrangement of the HASH1/ASCL1 gene.
Prognosis HASH1/ASCL1 is associated with significantly reduced survival in small cell lung carcinoma patients and has adverse prognostic association.
  
Entity Pheochromocytomas
Note Chromaffin tumors
Disease Because pheochromocytomas arise from chromaffin cells, they are occasionally called chromaffin tumors. Pheochromocytomas are found in the adrenal medulla. The adrenal medulla normally secretes two hormones, called norepinephrine and epinephrine(also known as adrenaline). Pheochromocytomas cause the adrenal medulla to secrete too much adrenaline and often causes the adrenal glands to make excess of hormones called catechol-amines which in turn causes high blood pressure and other symptoms.
Atleast in rat pheochromocytoma cell line PC12, MASH1/ASCL1 is readily detected which can be further induced by NGF treatment. Whether HASH1/ASCL1 also is over expressed in human cancers needs careful examination and distinction between tumor types.
Inheritance: About 10-25% of this cancer can be familial and mutations in genes e.g. VHL, RET, NF1, SDHB and SDHD are implicated.
Prognosis Pheochromocytoma can be potentially fatal, but it is relatively uncommon (2-8 cases per million people annually). As with other neuroendocrine tumors, high levels of HASH1/ASCL1 expression seen in pheochromocytomas correlate with poor prognosis. Activation of MEK1/MEK2-ERK1/ERK2 is necessary for differentiation of pheochromocytoma (PC12) cells and leads to decreased cell proliferation.
Cytogenetics Allelic losses at Chromosome 1p, 3p, 17p and 22q have been reported in sporadic and familial forms of pheochromocytomas.
  
Entity Gastrointestinal neuroendocrine carcinoma (NEC)
Disease Gastrointestinal NECs are defined as small cell carcinoma, morphologically similar to the small cell carcinoma of the lung. Gastrointestinal NE carcinoma (NEC) are extremely aggressive, but its pathophysiologic features remain poorly understood. Shida et al assessed HASH1/ASCL1 expression in human NECs by quantitative RT-PCR and in situ hybridisation and showed marked upregulation of HASH1/ASCL1 mRNA in NECs which was weak in carcinoid tumors and scarcely expressed in adenocarcinomas and normal mucosa.
Prognosis Levels of HASH1/ASCL1 can be used as a more sensitive and specific marker than conventional pan-endocrine markers for clinical diagnosis of gastrointestinal tumors to differentiate among gastrointestinal tumors particularly between carcinoids, adenocarcinomas and neuroendocrine gastrointestinal tumors in addition to other NE markers.
  
Entity Astrocytoma (secondary glioblastoma (GBM))
Note Glioblastoma
Disease Astrocytoma is the most common type of brain cancer arising from the astrocytes affecting cerebral hemispheres in adults and the brain stem in children accounting to almost 60% of brain tumors.
According to the world health organization, astrocytomas are classified in to four grades
1. Grade I or pilocytic astrocytoma (PA)
2. Grade II diffused astrocytoma (DA)
3. Grade III Anaplastic astrocyoma (AA)
4. Grade IV Glioblastoma multiforme (GBM)
GBM can further be classified as being primary or secondary based on the genetic mutations, age at occurrence, tendency of progression and clinical course. Familial clustering of gliomas is frequently observed associated with defined inherited tumor syndrome incuding the Li-Fraumeni syndrome, Turcot syndrome, and the NF1 syndrome. Several genes have been associated in distinguishing one or the other form of GBM notably among which are P53, MDM2, EGFR, CDK4. LOH on chromosome 9,10, 13, 17,19, 22 frequently occur in GBMs.
Prognosis The median survival time for a GBM individual is about 12 months and age at the time of occurrence plays a significant prognostic factor. Recently reported methylation at the O6- methyl guanine DNA methyl-transferase (MGMT) promoter has been shown to confer favourable prognostic value in terms of response to chemotherapy and longer survival. ASCL1 is highly upregulated in secondary GBMs as compared to the primary GBMs and can be thus ascribed as a distinguishing marker between the two. Concomitantly, there is repression of NOTCH1 signalling and HES1 expression in the secondary GBM. It is observed that primary GBM patients show rapid tumor progression and poor prognosis.
  

Other Solid tumors implicated (Data extracted from papers in the Atlas)

Solid Tumors AmeloblastomID5945

External links

Nomenclature
HGNC (Hugo)ASCL1   738
Cards
AtlasASCL1ID713ch12q23
Entrez_Gene (NCBI)ASCL1  429  achaete-scute family bHLH transcription factor 1
GeneCards (Weizmann)ASCL1
Ensembl (Hinxton)ENSG00000139352 [Gene_View]  chr12:103351452-103354294 [Contig_View]  ASCL1 [Vega]
ICGC DataPortalENSG00000139352
AceView (NCBI)ASCL1
Genatlas (Paris)ASCL1
WikiGenes429
SOURCE (Princeton)NM_004316
Genomic and cartography
GoldenPath (UCSC)ASCL1  -  12q23.2   chr12:103351452-103354294 +  12q22-q23   [Description]    (hg19-Feb_2009)
EnsemblASCL1 - 12q22-q23 [CytoView]
Mapping of homologs : NCBIASCL1 [Mapview]
OMIM100790   209880   
Gene and transcription
Genbank (Entrez)AK290539 AW071836 BC001638 BC002341 BC003134
RefSeq transcript (Entrez)NM_004316
RefSeq genomic (Entrez)AC_000144 NC_000012 NC_018923 NG_008950 NT_029419 NW_001838061 NW_004929384
Consensus coding sequences : CCDS (NCBI)ASCL1
Cluster EST : UnigeneHs.703025 [ NCBI ]
CGAP (NCI)Hs.703025
Alternative Splicing : Fast-db (Paris)GSHG0006945
Alternative Splicing GalleryENSG00000139352
Gene ExpressionASCL1 [ NCBI-GEO ]     ASCL1 [ SEEK ]   ASCL1 [ MEM ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP50553 (Uniprot)
NextProtP50553  [Medical]
With graphics : InterProP50553
Splice isoforms : SwissVarP50553 (Swissvar)
Domaine pattern : Prosite (Expaxy)BHLH (PS50888)   
Domains : Interpro (EBI)ASH    bHLH_dom   
Related proteins : CluSTrP50553
Domain families : Pfam (Sanger)HLH (PF00010)   
Domain families : Pfam (NCBI)pfam00010   
Domain families : Smart (EMBL)HLH (SM00353)  
DMDM Disease mutations429
Blocks (Seattle)P50553
Human Protein AtlasENSG00000139352
Peptide AtlasP50553
HPRD00011
IPIIPI00032964   
Protein Interaction databases
DIP (DOE-UCLA)P50553
IntAct (EBI)P50553
FunCoupENSG00000139352
BioGRIDASCL1
InParanoidP50553
Interologous Interaction database P50553
IntegromeDBASCL1
STRING (EMBL)ASCL1
Ontologies - Pathways
Ontology : AmiGOtranscription factor binding transcription factor activity  neuron migration  noradrenergic neuron development  noradrenergic neuron fate commitment  DNA binding  double-stranded DNA binding  sequence-specific DNA binding transcription factor activity  protein binding  nucleus  transcription, DNA-templated  Notch signaling pathway  neuroblast fate determination  neuroblast proliferation  response to lithium ion  regulation of gene expression  oligodendrocyte development  spinal cord association neuron differentiation  spinal cord oligodendrocyte cell fate specification  vestibular nucleus development  cerebral cortex GABAergic interneuron differentiation  central nervous system neuron development  cerebral cortex development  neurogenesis  response to retinoic acid  protein homodimerization activity  neuronal cell body  negative regulation of apoptotic process  bHLH transcription factor binding  positive regulation of neuron apoptotic process  sequence-specific DNA binding  negative regulation of neuron differentiation  positive regulation of neuron differentiation  positive regulation of Notch signaling pathway  positive regulation of cell cycle  negative regulation of transcription, DNA-templated  positive regulation of transcription from RNA polymerase II promoter  sympathetic nervous system development  neuron fate specification  positive regulation of neurogenesis  musculoskeletal movement, spinal reflex action  response to folic acid  subpallium neuron fate commitment  regulation of timing of subpallium neuron differentiation  olfactory pit development  lung epithelial cell differentiation  ventral spinal cord interneuron fate commitment  lung neuroendocrine cell differentiation  stomach neuroendocrine cell differentiation  carotid body glomus cell differentiation  adrenal chromaffin cell differentiation  sympathetic ganglion development  response to epidermal growth factor  E-box binding  cellular response to magnetism  positive regulation of neural precursor cell proliferation  
Ontology : EGO-EBItranscription factor binding transcription factor activity  neuron migration  noradrenergic neuron development  noradrenergic neuron fate commitment  DNA binding  double-stranded DNA binding  sequence-specific DNA binding transcription factor activity  protein binding  nucleus  transcription, DNA-templated  Notch signaling pathway  neuroblast fate determination  neuroblast proliferation  response to lithium ion  regulation of gene expression  oligodendrocyte development  spinal cord association neuron differentiation  spinal cord oligodendrocyte cell fate specification  vestibular nucleus development  cerebral cortex GABAergic interneuron differentiation  central nervous system neuron development  cerebral cortex development  neurogenesis  response to retinoic acid  protein homodimerization activity  neuronal cell body  negative regulation of apoptotic process  bHLH transcription factor binding  positive regulation of neuron apoptotic process  sequence-specific DNA binding  negative regulation of neuron differentiation  positive regulation of neuron differentiation  positive regulation of Notch signaling pathway  positive regulation of cell cycle  negative regulation of transcription, DNA-templated  positive regulation of transcription from RNA polymerase II promoter  sympathetic nervous system development  neuron fate specification  positive regulation of neurogenesis  musculoskeletal movement, spinal reflex action  response to folic acid  subpallium neuron fate commitment  regulation of timing of subpallium neuron differentiation  olfactory pit development  lung epithelial cell differentiation  ventral spinal cord interneuron fate commitment  lung neuroendocrine cell differentiation  stomach neuroendocrine cell differentiation  carotid body glomus cell differentiation  adrenal chromaffin cell differentiation  sympathetic ganglion development  response to epidermal growth factor  E-box binding  cellular response to magnetism  positive regulation of neural precursor cell proliferation  
Protein Interaction DatabaseASCL1
Wikipedia pathwaysASCL1
Gene fusion - rearrangments
Polymorphisms : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)ASCL1
SNP (GeneSNP Utah)ASCL1
SNP : HGBaseASCL1
Genetic variants : HAPMAPASCL1
1000_GenomesASCL1 
ICGC programENSG00000139352 
CONAN: Copy Number AnalysisASCL1 
Somatic Mutations in Cancer : COSMICASCL1 
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
Mutations and Diseases : HGMDASCL1
OMIM100790    209880   
MedgenASCL1
GENETestsASCL1
Disease Genetic AssociationASCL1
Huge Navigator ASCL1 [HugePedia]  ASCL1 [HugeCancerGEM]
Genomic VariantsASCL1  ASCL1 [DGVbeta]
Exome VariantASCL1
dbVarASCL1
ClinVarASCL1
snp3D : Map Gene to Disease429
General knowledge
Homologs : HomoloGeneASCL1
Homology/Alignments : Family Browser (UCSC)ASCL1
Phylogenetic Trees/Animal Genes : TreeFamASCL1
Chemical/Protein Interactions : CTD429
Chemical/Pharm GKB GenePA25038
Clinical trialASCL1
Cancer Resource (Charite)ENSG00000139352
Other databases
Probes
Litterature
PubMed72 Pubmed reference(s) in Entrez
CoreMineASCL1
iHOPASCL1

Bibliography

Localization of the human achaete-scute homolog gene (ASCL1) distal to phenylalanine hydroxylase (PAH) and proximal to tumor rejection antigen (TRA1) on chromosome 12q22-q23.
Renault B, Lieman J, Ward D, Krauter K, Kucherlapati R
Genomics. 1995 ; 30 (1) : 81-83.
PMID 8595908
 
An achaete-scute homologue essential for neuroendocrine differentiation in the lung.
Borges M, Linnoila RI, van de Velde HJ, Chen H, Nelkin BD, Mabry M, Baylin SB, Ball DW
Nature. 1997 ; 386 (6627) : 852-855.
PMID 9126746
 
Tissue-specific expression of human achaete-scute homologue-1 in neuroendocrine tumors: transcriptional regulation by dual inhibitory regions.
Chen H, Biel MA, Borges MW, Thiagalingam A, Nelkin BD, Baylin SB, Ball DW
Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research. 1997 ; 8 (6) : 677-686.
PMID 9186001
 
Constitutive achaete-scute homologue-1 promotes airway dysplasia and lung neuroendocrine tumors in transgenic mice.
Linnoila RI, Zhao B, DeMayo JL, Nelkin BD, Baylin SB, DeMayo FJ, Ball DW
Cancer research. 2000 ; 60 (15) : 4005-4009.
PMID 10945598
 
Large de novo deletion in chromosome 12 affecting the PAH, IGF1, ASCL1, and TRA1 genes.
Mallolas J, Vilaseca MA, Pavia C, Lambruschini N, Cambra FJ, Campistol J, Gˆ„mez D, Carriˆ„ A, Estivill X, MilˆÝ M
Journal of molecular medicine (Berlin, Germany). 2001 ; 78 (12) : 721-724.
PMID 11434725
 
Notch signaling induces rapid degradation of achaete-scute homolog 1.
Sriuranpong V, Borges MW, Strock CL, Nakakura EK, Watkins DN, Blaumueller CM, Nelkin BD, Ball DW
Molecular and cellular biology. 2002 ; 22 (9) : 3129-3139.
PMID 11940670
 
Quantitative reverse transcription-polymerase chain reaction measurement of HASH1 (ASCL1), a marker for small cell lung carcinomas with neuroendocrine features.
Westerman BA, Neijenhuis S, Poutsma A, Steenbergen RD, Breuer RH, Egging M, van Wijk IJ, Oudejans CB
Clinical cancer research : an official journal of the American Association for Cancer Research. 2002 ; 8 (4) : 1082-1086.
PMID 11948117
 
Widespread defects in the primary olfactory pathway caused by loss of Mash1 function.
Murray RC, Navi D, Fesenko J, Lander AD, Calof AL
The Journal of neuroscience : the official journal of the Society for Neuroscience. 2003 ; 23 (5) : 1769-1780.
PMID 12629181
 
The role of human achaete-scute homolog-1 in medullary thyroid cancer cells.
Sippel RS, Carpenter JE, Kunnimalaiyaan M, Chen H
Surgery. 2003 ; 134 (6) : 866-871.
PMID 14668716
 
The Notch signaling cascade in neuroblastoma: role of the basic helix-loop-helix proteins HASH-1 and HES-1.
Axelson H
Cancer letters. 2004 ; 204 (2) : 171-178.
PMID 15013216
 
Achaete-scute homolog-1 and Notch in lung neuroendocrine development and cancer.
Ball DW
Cancer letters. 2004 ; 204 (2) : 159-169.
PMID 15013215
 
RNA interference of achaete-scute homolog 1 in mouse prostate neuroendocrine cells reveals its gene targets and DNA binding sites.
Hu Y, Wang T, Stormo GD, Gordon JI
Proceedings of the National Academy of Sciences of the United States of America. 2004 ; 101 (15) : 5559-5564.
PMID 15060276
 
hASH1 expression is closely correlated with endocrine phenotype and differentiation extent in pulmonary neuroendocrine tumors.
Jiang SX, Kameya T, Asamura H, Umezawa A, Sato Y, Shinada J, Kawakubo Y, Igarashi T, Nagai K, Okayasu I
Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc. 2004 ; 17 (2) : 222-229.
PMID 14657947
 
Human achaete-scute homologue (hASH1) mRNA level as a diagnostic marker to distinguish esthesioneuroblastoma from poorly differentiated tumors arising in the sinonasal tract.
Mhawech P, Berczy M, Assaly M, Herrmann F, Bouzourene H, Allal AS, Dulguerov P, Schwaller J
American journal of clinical pathology. 2004 ; 122 (1) : 100-105.
PMID 15272537
 
Ascl1/Mash1 is required for the development of central serotonergic neurons.
Pattyn A, Simplicio N, van Doorninck JH, Goridis C, Guillemot F, Brunet JF
Nature neuroscience. 2004 ; 7 (6) : 589-595.
PMID 15133515
 
Ubiquilin-1 is a novel HASH-1-complexing protein that regulates levels of neuronal bHLH transcription factors in human neuroblastoma cells.
Persson P, Stockhausen MT, Pˆ€hlman S, Axelson H
International journal of oncology. 2004 ; 25 (5) : 1213-1221.
PMID 15492808
 
Medullary thyroid cancer: the functions of raf-1 and human achaete-scute homologue-1.
Chen H, Kunnimalaiyaan M, Van Gompel JJ
Thyroid : official journal of the American Thyroid Association. 2005 ; 15 (6) : 511-521.
PMID 16029117
 
Genetic association analyses of PHOX2B and ASCL1 in neuropsychiatric disorders: evidence for association of ASCL1 with Parkinson's disease.
Ide M, Yamada K, Toyota T, Iwayama Y, Ishitsuka Y, Minabe Y, Nakamura K, Hattori N, Asada T, Mizuno Y, Mori N, Yoshikawa T
Human genetics. 2005 ; 117 (6) : 520-527.
PMID 16021468
 
ASH1 gene is a specific therapeutic target for lung cancers with neuroendocrine features.
Osada H, Tatematsu Y, Yatabe Y, Horio Y, Takahashi T
Cancer research. 2005 ; 65 (23) : 10680-10685.
PMID 16322211
 
Aberrant expression of human achaete-scute homologue gene 1 in the gastrointestinal neuroendocrine carcinomas.
Shida T, Furuya M, Nikaido T, Kishimoto T, Koda K, Oda K, Nakatani Y, Miyazaki M, Ishikura H
Clinical cancer research : an official journal of the American Association for Cancer Research. 2005 ; 11 (2 Pt 1) : 450-458.
PMID 15701827
 
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Overexpression of the NOTCH1 intracellular domain inhibits cell proliferation and alters the neuroendocrine phenotype of medullary thyroid cancer cells.
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Mash1 is required for generic and subtype differentiation of hypothalamic neuroendocrine cells.
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Expression of oligodendroglial and astrocytic lineage markers in diffuse gliomas: use of YKL-40, ApoE, ASCL1, and NKX2-2.
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Gene expression profiles of small-cell lung cancers: molecular signatures of lung cancer.
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Written07-2007Jayashree S. Ladha, M R S Rao
Jawaharlal Nehru Centre for Advanced Scientific Research (A Deemed University) Jakkur P.O., Bangalore-560064, India

Citation

This paper should be referenced as such :
Ladha, JS ; Rao, MRS
ASCL1 (achaete-scute homolog 1 or achaete-scute complex homolog 1)
Atlas Genet Cytogenet Oncol Haematol. 2008;12(1):27-32.
Free online version   Free pdf version   [Bibliographic record ]
URL : http://AtlasGeneticsOncology.org/Genes/ASCL1ID713ch12q23.html

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