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MLLT10 (myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog, Drosophila); translocated to, 10)

Written1997-12Jean-Loup Huret
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France
Updated2005-10Cristina Morerio, Claudio Panarello
Dipartimento di Ematologia ed Oncologia Pediatrica, IRCCS Istituto Giannina Gaslini, Largo G. Gaslini 5, 16147 Genoa, Italy

(Note : for Links provided by Atlas : click)

Identity

Alias_namesmyeloid/lymphoid or mixed-lineage leukemia (trithorax (Drosophila) homolog); translocated to, 10
myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog, Drosophila); translocated to, 10
Alias_symbol (synonym)AF10
Other aliasAF10 (ALL1 fused gene from chromosome 10)
HGNC (Hugo) MLLT10
LocusID (NCBI) 8028
Atlas_Id 4
Location 10p12.31  [Link to chromosome band 10p12]
Location_base_pair Starts at 21534645 and ends at 21743630 bp from pter ( according to hg19-Feb_2009)  [Mapping MLLT10.png]
 
  AF10 (10p12) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics.
Fusion genes
(updated 2017)		Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
CDK6 (7q21.2) / MLLT10 (10p12.31)CLP1 (11q12.1) / MLLT10 (10p12.31)DDX3X (Xp11.4) / MLLT10 (10p12.31)
HNRNPH1 (5q35.3) / MLLT10 (10p12.31)KMT2A (11q23.3) / MLLT10 (10p12.31)KMT2B (19q13.12) / MLLT10 (10p12.31)
MLLT10 (10p12.31) / CACNA2D3 (3p21.1)MLLT10 (10p12.31) / CDK6 (7q21.2)MLLT10 (10p12.31) / CEP164 (11q23.3)
MLLT10 (10p12.31) / CLP1 (11q12.1)MLLT10 (10p12.31) / CNTNAP3B (9p11.2)MLLT10 (10p12.31) / CYTH1 (17q25.3)
MLLT10 (10p12.31) / DDX3X (Xp11.4)MLLT10 (10p12.31) / KCNJ6 (21q22.13)MLLT10 (10p12.31) / KMT2A (11q23.3)
MLLT10 (10p12.31) / LRCH3 (3q29)MLLT10 (10p12.31) / PICALM (11q14.2)MLLT10 (10p12.31) / PPP2R1B (11q23.1)
MLLT10 (10p12.31) / RACK1 (5q35.3)MLLT10 (10p12.31) / RNF169 (11q13.4)MLLT10 (10p12.31) / SGMS1 (10q11.23)
MLLT10 (10p12.31) / SNAP91 (6q14.2)MLLT10 (10p12.31) / SNTG1 (8q11.21)NAP1L1 (12q21.2) / MLLT10 (10p12.31)
PICALM (11q14.2) / MLLT10 (10p12.31)SNAP91 (6q14.2) / MLLT10 (10p12.31)USP54 (10q22.2) / MLLT10 (10p12.31)
XPO1 (2p15) / MLLT10 (10p12.31)

DNA/RNA

Transcription 5' telomeric --> 3' centromeric direction; 5.5 kb mRNA; coding sequence: 3.1 kb

Protein

 
  Representation of the AF10 protein modified by Linder B et al. J Mol Biol 2000 and Jones LK et al. Leukemia 2001.
Description 1027 amino acids; 109 KDa; N-term - LAP (leukemia associated protein)/PHD finger - Ext-LAP/PHD (Cys-rich region) - NLS (nuclear localisation signal) - AT-hook - LZ (leucine zipper) - Gln-rich domain - C-term
Expression mainly in the testis
Localisation nuclear
Function transcription factor
Homology with AF17 and BR140

Implicated in

Note
  
Entity t(10;11)(p12;q23)/AML -->KMT2A-MLLT10
Disease mainly M4/M5 AML
Cytogenetics Due to the opposite orientation of AF10 and MLL on their respective chromosome arms, MLL-AF10 gene fusion requires complex rearrangements with three or more breakpoints. An inversion of the 5'MLL or 3'AF10 is required in order to allow an in-frame MLL-AF10 fusion.
Hybrid/Mutated Gene 5' MLL - 3' AF10; breakpoints are at variable places along AF10
Abnormal Protein The AF10 Ext-LAP/PHD is always deleted, as are the MLL PHD fingers. Both retain the C-term LZ domain necessary for malignant transformation.
  
  
Entity inv ins(10;11)(p12;q23q12)/AML -->KMT2A - MLLT10
Disease One case of pediatric M5 AML
Hybrid/Mutated Gene 5' MLL - 3' AF10 and 5' AF10 - 3' HEAB, a gene at 11q12
Abnormal Protein only MLL-AF10 is expressed
  
  
Entity t(10;11)(p13;q14-21)-->CALM-MLLT10 and/or AF10-CALM
Disease Present both in myeloid and non myeloid acute leukemias: in T-cell ALL specific to TCRgd lineage; in myeloid leukemia described in FAB M0-AML, M1-AML, M5-AML, M7-AML.
Prognosis poor
Cytogenetics may well be confused with the above t(10;11)(p12;q23)
Hybrid/Mutated Gene 5' CALM - 3' AF10 and 5' AF10 - 3' CALM
In a 5' breakpoint cluster region (nucleotides 424 and 589), AF10 sequences retained the Ext-LAP/PHD domain. The presence of these kind of sequences seems to be necessary for maturation toward the TCRgd lineage, whereas their absence leads to maturation arrest at a more immature stage.
Abnormal Protein both CALM-AF10 and the reciprocal AF10-CALM are expressed. However, the CALM-AF10 contains most of the functional domains present in each of the two proteins.
  

Breakpoints

 
Note the breakpoint in the t(10;11)(p13;q14-21) is more in 5' of AF10

Bibliography

CALM-AF10 is a common fusion transcript in T-ALL and is specific to the TCRgammadelta lineage.
Asnafi V, Radford-Weiss I, Dastugue N, Bayle C, Leboeuf D, Charrin C, Garand R, Lafage-Pochitaloff M, Delabesse E, Buzyn A, Troussard X, Macintyre E
Blood. 2003 ; 102 (3) : 1000-1006.
PMID 12676784
 
Molecular basis of 11q23 rearrangements in hematopoietic malignant proliferations.
Bernard OA, Berger R
Genes, chromosomes & cancer. 1995 ; 13 (2) : 75-85.
PMID 7542910
 
Molecular analysis of the CALM/AF10 fusion: identical rearrangements in acute myeloid leukemia, acute lymphoblastic leukemia and malignant lymphoma patients.
Bohlander SK, Muschinsky V, Schrader K, Siebert R, Schlegelberger B, Harder L, Schemmel V, Fonatsch C, Ludwig WD, Hiddemann W, Dreyling MH
Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2000 ; 14 (1) : 93-99.
PMID 10637482
 
The t(10;11) translocation in acute myeloid leukemia (M5) consistently fuses the leucine zipper motif of AF10 onto the HRX gene.
Chaplin T, Bernard O, Beverloo HB, Saha V, Hagemeijer A, Berger R, Young BD
Blood. 1995 ; 86 (6) : 2073-2076.
PMID 7662954
 
Molecular analysis of the genomic inversion and insertion of AF10 into MLL suggests a single-step event.
Chaplin T, Jones L, Debernardi S, Hill AS, Lillington DM, Young BD
Genes, chromosomes & cancer. 2001 ; 30 (2) : 175-180.
PMID 11135434
 
The AF10 leucine zipper is required for leukemic transformation of myeloid progenitors by MLL-AF10.
DiMartino JF, Ayton PM, Chen EH, Naftzger CC, Young BD, Cleary ML
Blood. 2002 ; 99 (10) : 3780-3785.
PMID 11986236
 
MLL and CALM are fused to AF10 in morphologically distinct subsets of acute leukemia with translocation t(10;11): both rearrangements are associated with a poor prognosis.
Dreyling MH, Schrader K, Fonatsch C, Schlegelberger B, Haase D, Schoch C, Ludwig W, Löffler H, Büchner T, Wörmann B, Hiddemann W, Bohlander SK
Blood. 1998 ; 91 (12) : 4662-4667.
PMID 9616163
 
Identification and molecular characterisation of a CALM-AF10 fusion in acute megakaryoblastic leukaemia.
Jones LK, Chaplin T, Shankar A, Neat M, Patel N, Samuel DP, Hill AS, Debernardi S, Bassini A, Young BD, Saha V
Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2001 ; 15 (6) : 910-914.
PMID 11417476
 
Hematologic malignancies with the t(10;11) (p13;q21) have the same molecular event and a variety of morphologic or immunologic phenotypes.
Kobayashi H, Hosoda F, Maseki N, Sakurai M, Imashuku S, Ohki M, Kaneko Y
Genes, chromosomes & cancer. 1997 ; 20 (3) : 253-259.
PMID 9365832
 
The t(10;11)(p12;q23) translocation in acute leukaemia: a cytogenetic and clinical study of 20 patients. European 11q23 Workshop participants.
Lillington DM, Young BD, Berger R, Martineau M, Moorman AV, Secker-Walker LM
Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 1998 ; 12 (5) : 801-804.
PMID 9593284
 
Expression pattern and cellular distribution of the murine homologue of AF10.
Linder B, Jones LK, Chaplin T, Mohd-Sarip A, Heinlein UA, Young BD, Saha V
Biochimica et biophysica acta. 1998 ; 1443 (3) : 285-296.
PMID 9878787
 
Biochemical analyses of the AF10 protein: the extended LAP/PHD-finger mediates oligomerisation.
Linder B, Newman R, Jones LK, Debernardi S, Young BD, Freemont P, Verrijzer CP, Saha V
Journal of molecular biology. 2000 ; 299 (2) : 369-378.
PMID 10860745
 
MLL-MLLT10 fusion gene in pediatric acute megakaryoblastic leukemia.
Morerio C, Rapella A, Tassano E, Rosanda C, Panarello C
Leukemia research. 2005 ; 29 (10) : 1223-1226.
PMID 16111539
 
11q23 rearrangements in acute leukemia.
Rubnitz JE, Behm FG, Downing JR
Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 1996 ; 10 (1) : 74-82.
PMID 8558942
 
Molecular cytogenetic analysis of 10;11 rearrangements in acute myeloid leukemia.
Van Limbergen H, Poppe B, Janssens A, De Bock R, De Paepe A, Noens L, Speleman F
Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2002 ; 16 (3) : 344-351.
PMID 11896537
 
Chromosome abnormalities in leukaemia: the 11q23 paradigm.
Young BD, Saha V
Cancer surveys. 1996 ; 28 : 225-245.
PMID 8977038
 

Citation

This paper should be referenced as such :
Morerio, C ; Panarello, C
MLLT10 (myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog, Drosophila); translocated to, 10)
Atlas Genet Cytogenet Oncol Haematol. 2006;10(2):65-67.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/AF10ID4.html
History of this paper:
Huret, JL. AF10 (ALL1 fused gene from chromosome 10). Atlas Genet Cytogenet Oncol Haematol. 1997;1(2):51-52.
http://documents.irevues.inist.fr/bitstream/handle/2042/32046/12-1997-AF10ID4.pdf

Other Leukemias implicated (Data extracted from papers in the Atlas) [ 14 ]
  11q23 rearrangements (KMT2A) in de novo childhood acute myeloid leukemia
11q23 rearrangements (KMT2A) in leukaemia
11q23 rearrangements (KMT2A) in therapy related leukaemias
Infant leukaemias::Congenital leukaemias::Neonatal leukaemias
t(6;11)(q27;q23) KMT2A/AFDN
inv(7)(p15q34) TRB/HOXA10::t(7;7)(p15;q34) TRB/HOXA10
t(7;14)(p15;q11) TRD/HOXA10
t(X;10)(p11;p12) DDX3X/MLLT10
t(10;11)(p13;q21) PICALM/MLLT10
t(10;11)(p12;q23) KMT2A/MLLT10
t(10;11)(p11.2;q23) KMT2A/ABI1
t(11;17)(q23;q12-21) KMT2A/MMLT6
t(11;19)(q13;p13) FSTL3/CCND1
T-lineage acute lymphoblastic leukemia (T-ALL)

External links

Nomenclature
HGNC (Hugo)MLLT10   16063
Cards
AtlasAF10ID4
Entrez_Gene (NCBI)MLLT10  8028  myeloid/lymphoid or mixed-lineage leukemia; translocated to, 10
AliasesAF10
GeneCards (Weizmann)MLLT10
Ensembl hg19 (Hinxton)ENSG00000078403 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000078403 [Gene_View]  chr10:21534645-21743630 [Contig_View]  MLLT10 [Vega]
ICGC DataPortalENSG00000078403
TCGA cBioPortalMLLT10
AceView (NCBI)MLLT10
Genatlas (Paris)MLLT10
WikiGenes8028
SOURCE (Princeton)MLLT10
Genetics Home Reference (NIH)MLLT10
Genomic and cartography
GoldenPath hg38 (UCSC)MLLT10  -     chr10:21534645-21743630 +  10p12.31   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)MLLT10  -     10p12.31   [Description]    (hg19-Feb_2009)
EnsemblMLLT10 - 10p12.31 [CytoView hg19]  MLLT10 - 10p12.31 [CytoView hg38]
Mapping of homologs : NCBIMLLT10 [Mapview hg19]  MLLT10 [Mapview hg38]
OMIM602409   
Gene and transcription
Genbank (Entrez)AB209755 AF060929 AF060934 AF060935 AF060936
RefSeq transcript (Entrez)NM_001009569 NM_001195626 NM_001195627 NM_001195628 NM_001195630 NM_001324296 NM_001324297 NM_004641
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)MLLT10
Cluster EST : UnigeneHs.30385 [ NCBI ]
CGAP (NCI)Hs.30385
Alternative Splicing GalleryENSG00000078403
Gene ExpressionMLLT10 [ NCBI-GEO ]   MLLT10 [ EBI - ARRAY_EXPRESS ]   MLLT10 [ SEEK ]   MLLT10 [ MEM ]
Gene Expression Viewer (FireBrowse)MLLT10 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)8028
GTEX Portal (Tissue expression)MLLT10
Human Protein AtlasENSG00000078403-MLLT10 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP55197   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP55197  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP55197
Splice isoforms : SwissVarP55197
PhosPhoSitePlusP55197
Domaine pattern : Prosite (Expaxy)EPHD (PS51805)    ZF_PHD_1 (PS01359)    ZF_PHD_2 (PS50016)   
Domains : Interpro (EBI)Zinc_finger_PHD-type_CS    Znf_FYVE_PHD    Znf_PHD    Znf_PHD-finger    Znf_RING/FYVE/PHD   
Domain families : Pfam (Sanger)
Domain families : Pfam (NCBI)
Domain families : Smart (EMBL)PHD (SM00249)  
Conserved Domain (NCBI)MLLT10
DMDM Disease mutations8028
Blocks (Seattle)MLLT10
PDB (SRS)5DAG    5DAH   
PDB (PDBSum)5DAG    5DAH   
PDB (IMB)5DAG    5DAH   
PDB (RSDB)5DAG    5DAH   
Structural Biology KnowledgeBase5DAG    5DAH   
SCOP (Structural Classification of Proteins)5DAG    5DAH   
CATH (Classification of proteins structures)5DAG    5DAH   
SuperfamilyP55197
Human Protein Atlas [tissue]ENSG00000078403-MLLT10 [tissue]
Peptide AtlasP55197
HPRD03874
IPIIPI00023464   IPI00941044   IPI00641100   IPI00816742   IPI00641226   IPI00550534   IPI00470780   IPI00643230   IPI00514978   
Protein Interaction databases
DIP (DOE-UCLA)P55197
IntAct (EBI)P55197
FunCoupENSG00000078403
BioGRIDMLLT10
STRING (EMBL)MLLT10
ZODIACMLLT10
Ontologies - Pathways
QuickGOP55197
Ontology : AmiGODNA binding  transcription factor activity, sequence-specific DNA binding  protein binding  nucleus  nucleoplasm  cytosol  transcription, DNA-templated  zinc ion binding  protein complex  positive regulation of transcription from RNA polymerase II promoter  
Ontology : EGO-EBIDNA binding  transcription factor activity, sequence-specific DNA binding  protein binding  nucleus  nucleoplasm  cytosol  transcription, DNA-templated  zinc ion binding  protein complex  positive regulation of transcription from RNA polymerase II promoter  
NDEx NetworkMLLT10
Atlas of Cancer Signalling NetworkMLLT10
Wikipedia pathwaysMLLT10
Orthology - Evolution
OrthoDB8028
GeneTree (enSembl)ENSG00000078403
Phylogenetic Trees/Animal Genes : TreeFamMLLT10
HOVERGENP55197
HOGENOMP55197
Homologs : HomoloGeneMLLT10
Homology/Alignments : Family Browser (UCSC)MLLT10
Gene fusions - Rearrangements
Fusion : MitelmanDDX3X/MLLT10 [Xp11.4/10p12.31]  [t(X;10)(p11;p12)]  
Fusion : MitelmanHNRNPH1/MLLT10 [5q35.3/10p12.31]  [t(5;10)(q35;p12)]  
Fusion : MitelmanMLLT10/CEP164 [10p12.31/11q23.3]  [t(10;11)(p12;q23)]  
Fusion : MitelmanMLLT10/CLP1 [10p12.31/11q12.1]  [ins(10;11)(p12;q23q12)]  [ins(10;11)(p12;q23q23)]  
Fusion : MitelmanMLLT10/DDX3X [10p12.31/Xp11.4]  [t(X;10)(p11;p12)]  
Fusion : MitelmanMLLT10/KCNJ6 [10p12.31/21q22.13]  [t(10;21)(p12;q22)]  
Fusion : MitelmanMLLT10/PICALM [10p12.31/11q14.2]  [t(10;11)(p12;q14)]  
Fusion : MitelmanMLLT10/PPP2R1B [10p12.31/11q23.1]  [t(10;11)(p12;q23)]  
Fusion : MitelmanMLLT10/RNF169 [10p12.31/11q13.4]  [t(10;11)(p12;q13)]  
Fusion : MitelmanMLLT10/SNTG1 [10p12.31/8q11.21]  [t(8;10)(q11;p12)]  
Fusion : MitelmanNAP1L1/MLLT10 [12q21.2/10p12.31]  [t(10;12)(p12;q21)]  
Fusion : MitelmanPICALM/MLLT10 [11q14.2/10p12.31]  [t(10;11)(p12;q14)]  [t(10;11)(p12;q23)]  
[t(10;19;11)(p12;p13;q14)]  [t(9;11)(p12;q14)]  
Fusion : MitelmanXPO1/MLLT10 [2p15/10p12.31]  [t(2;10)(p15;p12)]  
Fusion : COSMICKMT2A [11q23.3]  -  MLLT10 [10p12.31]  [fusion_2033]  [fusion_2034]  [fusion_2035]  [fusion_2036]  [fusion_2037]  [fusion_2038]  [fusion_2039]  
[fusion_2040]  [fusion_2041]  [fusion_2042]  [fusion_2043]  [fusion_2044]  [fusion_2045]  [fusion_2046]  [fusion_2047]  [fusion_2048]  [fusion_2049]  
[fusion_2050]  [fusion_2051]  [fusion_2052]  
Fusion: TCGAMLLT10 10p12.31 KCNJ6 21q22.13 LUAD
Fusion: TCGAMLLT10 10p12.31 PICALM 11q14.2 LAML
Fusion: TCGAMLLT10 10p12.31 SNTG1 8q11.21 BRCA
Fusion: TCGAMLL MLLT10 10p12.31 LAML
Fusion: TCGAPICALM 11q14.2 MLLT10 10p12.31 LAML
Fusion : TICdbKMT2A [11q23.3]  -  MLLT10 [10p12.31]
Fusion : TICdbPICALM [11q14.2]  -  MLLT10 [10p12.31]
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerMLLT10 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)MLLT10
dbVarMLLT10
ClinVarMLLT10
1000_GenomesMLLT10 
Exome Variant ServerMLLT10
ExAC (Exome Aggregation Consortium)ENSG00000078403
GNOMAD BrowserENSG00000078403
Genetic variants : HAPMAP8028
Genomic Variants (DGV)MLLT10 [DGVbeta]
DECIPHERMLLT10 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisMLLT10 
Mutations
ICGC Data PortalMLLT10 
TCGA Data PortalMLLT10 
Broad Tumor PortalMLLT10
OASIS PortalMLLT10 [ Somatic mutations - Copy number]
Cancer Gene: CensusMLLT10 
Somatic Mutations in Cancer : COSMICMLLT10  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDMLLT10
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch MLLT10
DgiDB (Drug Gene Interaction Database)MLLT10
DoCM (Curated mutations)MLLT10 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)MLLT10 (select a term)
intoGenMLLT10
NCG5 (London)MLLT10
Cancer3DMLLT10(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM602409   
Orphanet14434   
MedgenMLLT10
Genetic Testing Registry MLLT10
NextProtP55197 [Medical]
TSGene8028
GENETestsMLLT10
Target ValidationMLLT10
Huge Navigator MLLT10 [HugePedia]
snp3D : Map Gene to Disease8028
BioCentury BCIQMLLT10
ClinGenMLLT10
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD8028
Chemical/Pharm GKB GenePA30849
Clinical trialMLLT10
Miscellaneous
canSAR (ICR)MLLT10 (select the gene name)
Probes
Litterature
PubMed41 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineMLLT10
EVEXMLLT10
GoPubMedMLLT10
iHOPMLLT10
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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