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AKT3 (v-akt murine thymoma viral oncogene homolog 3, Protein Kinase B gamma)

Written2007-07Mitchell Cheung, Joseph R. Testa
Human Genetics Program, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111, USA

(Note : for Links provided by Atlas : click)


Alias (NCBI)DKFZP434N0250
HGNC (Hugo) AKT3
HGNC Alias symbPKBG
HGNC Alias name"protein kinase B, gamma"
HGNC Previous namev-akt murine thymoma viral oncogene homolog 3
LocusID (NCBI) 10000
Atlas_Id 615
Location 1q43  [Link to chromosome band 1q43]
Location_base_pair Starts at 243488233 and ends at 243843282 bp from pter ( according to GRCh38/hg38-Dec_2013)  [Mapping AKT3.png]
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
ACVR2A (2q22.3) / AKT3 (1q43)AKT3 (1q43) / AKT3 (1q43)AKT3 (1q43) / ANK3 (10q21.2)
AKT3 (1q43) / CEP170 (1q43)AKT3 (1q43) / GCSAML (1q44)AKT3 (1q43) / P2RX5 (17p13.2)
AKT3 (1q43) / PPP2R2A (8p21.2)AKT3 (1q43) / PVT1 (8q24.21)AKT3 (1q43) / RGS7 (1q43)
CNOT6L (4q21.1) / AKT3 (1q43)GOLPH3L (1q21.3) / AKT3 (1q43)MAGI3 (1p13.2) / AKT3 (1q43)
RAC1 (7p22.1) / AKT3 (1q43)WDR20 (14q32.31) / AKT3 (1q43)
Note Location in the mouse: chromosome 1 in band H4-H6


Description The AKT3 gene is composed of 14 exons spanning a genomic region of 354,937 bp.
Transcription AKT3 coding sequence consists of 1,440 bp from the start codon to the stop codon.


  Diagram of the AKT3 protein in scale. The numbers represent specific residues. The domains are PH (Pleckstrin Homology), a short helical region, Kinase (Catalytic Kinase), and Regulatory (Regulatory Region). Indicated are the two phosphorylation sites shown to be essential for activation of AKT3: Threonine 305 and serine 472. C: Carboxyl-terminal; N: Amino-terminal.
Description The AKT3 serine/threonine kinase consists of 479 amino acids with a calculated molecular weight of 55.8 kDa (approximate molecular weight of 59-60 kDa seen on a Western blot). The protein contains three important regions: the PH domain at the N terminus (residues 1-107), a kinase domain (residues 148-405), and a C-terminal regulatory domain (residues 406-479). A 465-amino acid splice variant lacking the serine 472 residue has been identified, which results from alternative splicing of an exon at the C terminus.
Expression Northern blot analysis of AKT3 indicated that it is expressed in virtually all tissues, predominantly in the brain and fetal heart and at lower levels in liver and skeletal muscle. RT-PCR analysis also indicated expression of AKT3 in a wide variety of tissues.
Localisation Predominantly cytoplasmic; also found at the plasma membrane and in the nucleus following its activation.
Function AKT family members are serine/threonine kinases activated following stimulation by growth factors, hormones and the extracellular matrix. AKT kinases play a key role in proliferation, cell survival, and tumorigenesis. Binding of ligands (e.g., EGF) to tyrosine kinase receptors or G-protein coupled receptors leads to the recruitment and activation of the Class 1A and Class 1B PI3K (Phosphatidylinositol 3-Kinase), respectively. The pleckstrin homology domain of AKT kinases has affinity for the 3'-phosphorylated phosphoinositides 3,4,5-trisphosphate (PI-3,4,5-P3) and PI-3,4-P2 produced by PI3K, and they are activated specifically by the latter lipid. Phospholipid binding triggers the translocation of AKT kinases to the plasma membrane. There, AKT is activated through phosphorylation of a threonine (T308 in AKT1, T309 in AKT2 and T305 in AKT3) by PDK1 and on a serine (S473 on AKT1, S474 on AKT2, and S472 on AKT3) by PDK2. Activated AKT then phosphorylates a number of different substrates involved in survival, cell cycle progression, and other pathways implicated in tumorigenesis.
Homology AKT3 is a serine/threonine kinase and is a member of the AKT family that also includes AKT1 and AKT2. At the protein level, AKT3 shows overall 83.6% identity with AKT1 and 78% identity with AKT2. The three AKT kinases are identical in the ATP binding region, except for one residue: Ala 230 of AKT1 is conserved in AKT2 (Ala 232), but switches to Val 228 in AKT3.


Note No germline or somatic mutations were discovered through sequencing.

Implicated in

Entity Breast Cancer
Oncogenesis AKT3 was found to be expressed at a higher level in estrogen receptor-negative breast cancer compared to estrogen receptor-positive cancers, thus possibly contributing to the more aggressive phenotype of the former. AKT3 activity was also 30-to 60-fold higher in two estrogen receptor-negative cell lines as compared to two estrogen receptor-positive cell lines.
Entity Hepatocellular carcinoma (Hepatitis C virus related)
Oncogenesis Using array-CGH analysis, gene copy number increases of AKT3 were found in 6 out of 19 (32%) tumors, including small, well-differentiated carcinomas. Thus, increased copies of the gene may play a potentially important role in the onset of Hepatitis C-related hepatocellular carcinoma.
Entity Melanoma
Oncogenesis AKT3 was demonstrated to be the predominant AKT isoform involved in melanoma tumorigenesis. Knockdown of AKT3 with siRNA was shown to decrease total phospho-AKT levels in four melanoma cell lines and in normal melanocytes. In contrast, targeting the other two AKT proteins had no effect. AKT3 protein was overexpressed in 60% of primary melanoma tumors compared to normal melanocytes. Immunoprecipitation of AKT3 followed by immunoblotting with a phospho-specific AKT antibody indicated that 43% of primary melanomas have increased AKT3 activity compared to normal controls. Moreover, siRNA-mediated knockdown of AKT3 in a melanoma cell line led to a dramatic decrease in xenograft tumor size as a result of increased apoptosis.
Entity Ovarian Cancer
Oncogenesis AKT3 was discovered to be highly expressed in 19 out of 92 (20%) primary ovarian tumors and also expressed in a number of ovarian tumor cell lines, including two cell lines having duplications of the AKT3 gene. The high expression of AKT3 in cell lines appeared to correlate with high total phospho-AKT levels, increased proliferation, and the ability to grow in serum starved conditions. SiRNA-mediated silencing of AKT3 expression in the OVCA429 and DOV13 cell lines resulted in reduced proliferation due to inhibition of the cell cycle.
Entity Prostate Cancer
Oncogenesis AKT3 was found to be expressed at a higher level and with a 20- to 40-fold higher activity in androgen-insensitive prostate cancer compared to androgen-sensitive prostate cancer. The loss of PTEN expression appeared to contribute to increased AKT3 activity in one of the cell lines examined. Thus, AKT3 may play a role in the more aggressive phenotype of androgen-insensitive prostate cancers.


Perturbations of the AKT signaling pathway in human cancer.
Altomare DA, Testa JR
Oncogene. 2005 ; 24 (50) : 7455-7464.
PMID 16288292
A portrait of AKT kinases: human cancer and animal models depict a family with strong individualities.
Bellacosa A, Testa JR, Moore R, Larue L
Cancer biology & therapy. 2004 ; 3 (3) : 268-275.
PMID 15034304
Two splice variants of protein kinase B gamma have different regulatory capacity depending on the presence or absence of the regulatory phosphorylation site serine 472 in the carboxyl-terminal hydrophobic domain.
Brodbeck D, Hill MM, Hemmings BA
The Journal of biological chemistry. 2001 ; 276 (31) : 29550-29558.
PMID 11387345
A specific role for AKT3 in the genesis of ovarian cancer through modulation of G(2)-M phase transition.
Cristiano BE, Chan JC, Hannan KM, Lundie NA, Marmy-Conus NJ, Campbell IG, Phillips WA, Robbie M, Hannan RD, Pearson RB
Cancer research. 2006 ; 66 (24) : 11718-11725.
PMID 17178867
Analysis of DNA copy number aberrations in hepatitis C virus-associated hepatocellular carcinomas by conventional CGH and array CGH.
Hashimoto K, Mori N, Tamesa T, Okada T, Kawauchi S, Oga A, Furuya T, Tangoku A, Oka M, Sasaki K
Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc. 2004 ; 17 (6) : 617-622.
PMID 15133472
Molecular cloning, expression and characterization of the human serine/threonine kinase Akt-3.
Masure S, Haefner B, Wesselink JJ, Hoefnagel E, Mortier E, Verhasselt P, Tuytelaars A, Gordon R, Richardson A
European journal of biochemistry / FEBS. 1999 ; 265 (1) : 353-360.
PMID 10491192
Mapping of AKT3, encoding a member of the Akt/protein kinase B family, to human and rodent chromosomes by fluorescence in situ hybridization.
Murthy SS, Tosolini A, Taguchi T, Testa JR
Cytogenetics and cell genetics. 2000 ; 88 (1-2) : 38-40.
PMID 10773662
Up-regulation of Akt3 in estrogen receptor-deficient breast cancers and androgen-independent prostate cancer lines.
Nakatani K, Thompson DA, Barthel A, Sakaue H, Liu W, Weigel RJ, Roth RA
The Journal of biological chemistry. 1999 ; 274 (31) : 21528-21532.
PMID 10419456
Deregulated Akt3 activity promotes development of malignant melanoma.
Stahl JM, Sharma A, Cheung M, Zimmerman M, Cheng JQ, Bosenberg MW, Kester M, Sandirasegarane L, Robertson GP
Cancer research. 2004 ; 64 (19) : 7002-7010.
PMID 15466193
AKT-1, -2, and -3 are expressed in both normal and tumor tissues of the lung, breast, prostate, and colon.
Zinda MJ, Johnson MA, Paul JD, Horn C, Konicek BW, Lu ZH, Sandusky G, Thomas JE, Neubauer BL, Lai MT, Graff JR
Clinical cancer research : an official journal of the American Association for Cancer Research. 2001 ; 7 (8) : 2475-2479.
PMID 11489829


This paper should be referenced as such :
Cheung, M ; Testa, JR
AKT3 (v-akt murine thymoma viral oncogene homolog 3, Protein Kinase B gamma)
Atlas Genet Cytogenet Oncol Haematol. 2008;12(1):24-26.
Free journal version : [ pdf ]   [ DOI ]

Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 4 ]
  t(1;1)(p13;q44) MAGI3/AKT3
t(1;2)(q44;q22) ACVR2A/AKT3
t(1;8)(q44;p21) AKT3/PPP2R2A
t(1;8)(q44;q24) AKT3/PVT1

External links

HGNC (Hugo)AKT3   393
Entrez_Gene (NCBI)AKT3    AKT serine/threonine kinase 3
PRKBG; RAC-PK-gamma; RAC-gamma; STK-2
GeneCards (Weizmann)AKT3
Ensembl hg19 (Hinxton)ENSG00000117020 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000117020 [Gene_View]  ENSG00000117020 [Sequence]  chr1:243488233-243843282 [Contig_View]  AKT3 [Vega]
ICGC DataPortalENSG00000117020
TCGA cBioPortalAKT3
AceView (NCBI)AKT3
Genatlas (Paris)AKT3
SOURCE (Princeton)AKT3
Genetics Home Reference (NIH)AKT3
Genomic and cartography
GoldenPath hg38 (UCSC)AKT3  -     chr1:243488233-243843282 -  1q43-q44   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)AKT3  -     1q43-q44   [Description]    (hg19-Feb_2009)
GoldenPathAKT3 - 1q43-q44 [CytoView hg19]  AKT3 - 1q43-q44 [CytoView hg38]
genome Data Viewer NCBIAKT3 [Mapview hg19]  
OMIM611223   615937   
Gene and transcription
Genbank (Entrez)AF085234 AF124141 AF135794 AJ245709 AK055109
RefSeq transcript (Entrez)NM_001206729 NM_001370074 NM_005465 NM_181690
RefSeq genomic (Entrez)NC_000001 NG_029764 NT_187519
Consensus coding sequences : CCDS (NCBI)AKT3
Alternative Splicing GalleryENSG00000117020
Gene ExpressionAKT3 [ NCBI-GEO ]   AKT3 [ EBI - ARRAY_EXPRESS ]   AKT3 [ SEEK ]   AKT3 [ MEM ]
Gene Expression Viewer (FireBrowse)AKT3 [ Firebrowse - Broad ]
GenevisibleExpression of AKT3 in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)10000
GTEX Portal (Tissue expression)AKT3
Human Protein AtlasENSG00000117020-AKT3 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ9Y243   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ9Y243  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ9Y243
Splice isoforms : SwissVarQ9Y243
Catalytic activity : Enzyme2.7.11.1 [ Enzyme-Expasy ] [ IntEnz-EBI ] [ BRENDA ] [ KEGG ]   [ MEROPS ]
Domaine pattern : Prosite (Expaxy)AGC_KINASE_CTER (PS51285)    PH_DOMAIN (PS50003)    PROTEIN_KINASE_ATP (PS00107)    PROTEIN_KINASE_DOM (PS50011)    PROTEIN_KINASE_ST (PS00108)   
Domains : Interpro (EBI)AGC-kinase_C    Akt3    Kinase-like_dom_sf    PH-like_dom_sf    PH_domain    PH_PKB    Pkinase_C    Prot_kinase_dom    Protein_kinase_ATP_BS    RAC_gamma-like    Ser/Thr_kinase_AS   
Domain families : Pfam (Sanger)PH (PF00169)    Pkinase (PF00069)    Pkinase_C (PF00433)   
Domain families : Pfam (NCBI)pfam00169    pfam00069    pfam00433   
Domain families : Smart (EMBL)PH (SM00233)  S_TK_X (SM00133)  S_TKc (SM00220)  
Conserved Domain (NCBI)AKT3
Blocks (Seattle)AKT3
PDB (RSDB)2X18   
PDB Europe2X18   
PDB (PDBSum)2X18   
PDB (IMB)2X18   
Structural Biology KnowledgeBase2X18   
SCOP (Structural Classification of Proteins)2X18   
CATH (Classification of proteins structures)2X18   
Human Protein Atlas [tissue]ENSG00000117020-AKT3 [tissue]
Peptide AtlasQ9Y243
IPIIPI00031747   IPI00219411   IPI01021636   
Protein Interaction databases
IntAct (EBI)Q9Y243
Ontologies - Pathways
Ontology : AmiGOmitochondrial genome maintenance  positive regulation of endothelial cell proliferation  protein kinase activity  protein serine/threonine kinase activity  protein serine/threonine kinase activity  protein binding  ATP binding  nucleus  cytoplasm  protein phosphorylation  signal transduction  membrane  peptidyl-serine phosphorylation  intracellular signal transduction  positive regulation of blood vessel endothelial cell migration  positive regulation of cell migration involved in sprouting angiogenesis  positive regulation of vascular endothelial cell proliferation  negative regulation of cellular senescence  
Ontology : EGO-EBImitochondrial genome maintenance  positive regulation of endothelial cell proliferation  protein kinase activity  protein serine/threonine kinase activity  protein serine/threonine kinase activity  protein binding  ATP binding  nucleus  cytoplasm  protein phosphorylation  signal transduction  membrane  peptidyl-serine phosphorylation  intracellular signal transduction  positive regulation of blood vessel endothelial cell migration  positive regulation of cell migration involved in sprouting angiogenesis  positive regulation of vascular endothelial cell proliferation  negative regulation of cellular senescence  
Pathways : KEGGMAPK signaling pathway    ErbB signaling pathway    Ras signaling pathway    Rap1 signaling pathway    Chemokine signaling pathway    HIF-1 signaling pathway    FoxO signaling pathway    mTOR signaling pathway    PI3K-Akt signaling pathway    Apoptosis    Adrenergic signaling in cardiomyocytes    VEGF signaling pathway    Osteoclast differentiation    Focal adhesion    Tight junction    Toll-like receptor signaling pathway    Jak-STAT signaling pathway    T cell receptor signaling pathway    B cell receptor signaling pathway    Fc epsilon RI signaling pathway    Fc gamma R-mediated phagocytosis    TNF signaling pathway    Neurotrophin signaling pathway    Cholinergic synapse    Dopaminergic synapse    Insulin signaling pathway    Progesterone-mediated oocyte maturation    Estrogen signaling pathway    Prolactin signaling pathway    Thyroid hormone signaling pathway    Adipocytokine signaling pathway    Non-alcoholic fatty liver disease (NAFLD)    Carbohydrate digestion and absorption    Chagas disease (American trypanosomiasis)    Toxoplasmosis    Tuberculosis    Hepatitis C    Hepatitis B    Measles    Influenza A    HTLV-I infection    Epstein-Barr virus infection    Pathways in cancer    Proteoglycans in cancer    Colorectal cancer    Renal cell carcinoma    Pancreatic cancer    Endometrial cancer    Glioma    Prostate cancer    Melanoma    Chronic myeloid leukemia    Acute myeloid leukemia    Small cell lung cancer    Non-small cell lung cancer   
REACTOMEQ9Y243 [protein]
REACTOME PathwaysR-HSA-9634638 [pathway]   
NDEx NetworkAKT3
Atlas of Cancer Signalling NetworkAKT3
Wikipedia pathwaysAKT3
Orthology - Evolution
GeneTree (enSembl)ENSG00000117020
Phylogenetic Trees/Animal Genes : TreeFamAKT3
Homologs : HomoloGeneAKT3
Homology/Alignments : Family Browser (UCSC)AKT3
Gene fusions - Rearrangements
Fusion : MitelmanACVR2A/AKT3 [2q22.3/1q43]  
Fusion : MitelmanAKT3/PPP2R2A [1q43/8p21.2]  
Fusion : MitelmanAKT3/PVT1 [1q43/8q24.21]  
Fusion : MitelmanMAGI3/AKT3 [1p13.2/1q43]  
Fusion PortalACVR2A 2q22.3 AKT3 1q43 PRAD
Fusion PortalAKT3 1q43 C1orf150 GBM
Fusion PortalAKT3 1q43 PPP2R2A 8p21.2 PRAD
Fusion PortalAKT3 1q43 RGS7 1q43 GBM
Fusion : FusionGDB2.7.11.1   
Fusion : Fusion_HubACVR2A--AKT3    AGPAT4--AKT3    AKT3--ADSS    AKT3--AKT3    AKT3--AMFR    AKT3--AMY2B    AKT3--ANGPTL2    AKT3--ANK3    AKT3--ARHGAP30    AKT3--ARPC2    AKT3--ASUN    AKT3--BLK    AKT3--BTBD1    AKT3--C1ORF150    AKT3--C1ORF21   
AKT3--CCNY    AKT3--CD55    AKT3--CEP170    AKT3--CFH    AKT3--CNOT6L    AKT3--DPYSL2    AKT3--EFCAB2    AKT3--EGLN1    AKT3--ENAH    AKT3--ETFA    AKT3--FAN1    AKT3--FEZ1    AKT3--FGFR1OP2    AKT3--FOCAD    AKT3--G3BP2   
AKT3--GIGYF2    AKT3--GNAS    AKT3--GOPC    AKT3--HEATR1    AKT3--HMGB1    AKT3--HNRNPDL    AKT3--HSD17B4    AKT3--IER3IP1    AKT3--KCNH1    AKT3--KCNT2    AKT3--KIF26B    AKT3--LYST    AKT3--MAGI3    AKT3--MARC2    AKT3--MEMO1   
AKT3--MOCS2    AKT3--MTIF3    AKT3--NDUFS6    AKT3--NR2C1    AKT3--NUCKS1    AKT3--P2RX5    AKT3--PCDH7    AKT3--PICALM    AKT3--PIK3R3    AKT3--PLD5    AKT3--PPP2R2A    AKT3--PRKRA    AKT3--PTPRR    AKT3--RBPJ    AKT3--RGS7   
AKT3--RHOQ    AKT3--RWDD1    AKT3--SDCCAG8    AKT3--SEC31A    AKT3--SF3B1    AKT3--SLC39A10    AKT3--SMIM13    AKT3--SON    AKT3--STRBP    AKT3--TBX18    AKT3--TFB2M    AKT3--TMEM168    AKT3--TRB@    AKT3--WASF1    AKT3--ZBTB18   
AKT3--ZEB2    AKT3--ZNF670    AKT3--ZZZ3    AMY2A--AKT3    APP--AKT3    CALCOCO2--AKT3    CAPZB--AKT3    CD46--AKT3    CEP170--AKT3    CNOT2--AKT3    CNOT6L--AKT3    CNST--AKT3    DNM3--AKT3    FIP1L1--AKT3    GOLPH3L--AKT3   
INHBA--AKT3    KCNK1--AKT3    KIF26B--AKT3    MAGI3--AKT3    MKL2--AKT3    NAP1L1--AKT3    NOVA1--AKT3    PGR--AKT3    RAC1--AKT3    RGS12--AKT3    ROCK1--AKT3    SETD3--AKT3    TAF1B--AKT3    THOC2--AKT3    TLK1--AKT3   
TMEM56--AKT3    TMEM57--AKT3    WDR20--AKT3    ZEB2--AKT3    ZNF385D--AKT3    ZNF670--AKT3    ZNF738--AKT3   
Fusion : QuiverAKT3
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerAKT3 [hg38]
Exome Variant ServerAKT3
GNOMAD BrowserENSG00000117020
Varsome BrowserAKT3
Genomic Variants (DGV)AKT3 [DGVbeta]
DECIPHERAKT3 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisAKT3 
ICGC Data PortalAKT3 
TCGA Data PortalAKT3 
Broad Tumor PortalAKT3
OASIS PortalAKT3 [ Somatic mutations - Copy number]
Cancer Gene: CensusAKT3 
Somatic Mutations in Cancer : COSMICAKT3  [overview]  [genome browser]  [tissue]  [distribution]  
Somatic Mutations in Cancer : COSMIC3DAKT3
Mutations and Diseases : HGMDAKT3
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch AKT3
DgiDB (Drug Gene Interaction Database)AKT3
DoCM (Curated mutations)AKT3 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)AKT3 (select a term)
NCG6 (London) select AKT3
Cancer3DAKT3(select the gene name)
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
OMIM611223    615937   
Orphanet11582    14375   
Genetic Testing Registry AKT3
NextProtQ9Y243 [Medical]
Target ValidationAKT3
Huge Navigator AKT3 [HugePedia]
Clinical trials, drugs, therapy
Protein Interactions : CTD
Pharm GKB GenePA24686
Pharm GKB PathwaysPA152530845   PA162356267   PA2032   
Clinical trialAKT3
canSAR (ICR)AKT3 (select the gene name)
DataMed IndexAKT3
PubMed201 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Fri Feb 19 17:45:25 CET 2021

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