Schematic overview of the cellular and molecular mechanisms involved in the cancer progression, including the proposed cellular and molecular mechanisms in cancer cells trajectory. AT1: alveolar type 1 cells; AT2: alveolar type 2 cells; AAH: atypical adenomatous hyperplasia; AIS: adenocarcinoma in situ; MIA: minimally invasive adenocarcinoma; IA: invasive adenocarcinoma; EMT: epithelial-mesenchymal transition

Home

Download

Statistics

Help

Contact

	Gene summary
	Malignant transformation analysis
	Malignant transformation related pathway analysis
	Cell-cell communication analysis
	Single-cell gene regulatory network inference analysis
	Somatic mutation of malignant transformation related genes
	Related drugs of malignant transformation related genes

Gene: DOT1L

Gene summary for DOT1L

Gene summary.

Gene information	Species	Human
	Gene symbol	DOT1L
	Gene ID	84444
	Gene name	DOT1 like histone lysine methyltransferase
	Gene Alias	DOT1
	Cytomap	19p13.3
	Gene Type	protein-coding
	GO ID	GO:0000075
	UniProtAcc	Q8TEK3

Top

Malignant transformation analysis

Identification of the aberrant gene expression in precancerous and cancerous lesions by comparing the gene expression of stem-like cells in diseased tissues with normal stem cells

Malignant transformation involving gene list.

Entrez ID	Symbol	Replicates	Species	Organ	Tissue	Adj P-value	Log2FC	Malignancy
84444	DOT1L	HCC1_Meng	Human	Liver	HCC	2.91e-08	-5.61e-02	0.0246
84444	DOT1L	HCC2_Meng	Human	Liver	HCC	4.39e-05	-3.52e-02	0.0107
84444	DOT1L	S014	Human	Liver	HCC	2.01e-03	2.78e-01	0.2254
84444	DOT1L	S027	Human	Liver	HCC	3.21e-12	8.06e-01	0.2446
84444	DOT1L	S028	Human	Liver	HCC	1.28e-10	5.00e-01	0.2503
84444	DOT1L	S029	Human	Liver	HCC	1.40e-06	4.36e-01	0.2581

Page: 1

Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Liver		HCC: Hepatocellular carcinoma
Liver		NAFLD: Non-alcoholic fatty liver disease

∗log2FC in expression of this searched gene in stem-like cells from each diseased tissue sample relative to stem-like cells in normal samples in each tissue plotted against the malignancy continuum. Samples are colored based on if they are from different disease stage.

Top

Malignant transformation related pathway analysis

Find out the enriched GO biological processes and KEGG pathways involved in transition from healthy to precancer to cancer

Figure of enriched GO biological processes.

Tissue	Disease Stage	Enriched GO biological Processes
Colorectum	AD
Colorectum	SER
Colorectum	MSS
Colorectum	MSI-H
Colorectum	FAP

∗Top 15 enriched GO BP terms are showed in the bar plot of each disease state in each tissue. Each row represents a significant GO biological process which is colored according to the -log10(p.adjust).

Page: 1 2 3 4 5 6 7 8 9

Enriched GO biological processes.

GO ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	Count
GO:001657021	Liver	HCC	histone modification	283/7958	463/18723	2.68e-16	2.33e-14	283
GO:005109822	Liver	HCC	regulation of binding	225/7958	363/18723	3.78e-14	2.37e-12	225
GO:00182052	Liver	HCC	peptidyl-lysine modification	230/7958	376/18723	1.51e-13	8.32e-12	230
GO:00434141	Liver	HCC	macromolecule methylation	183/7958	316/18723	2.00e-08	4.72e-07	183
GO:0032259	Liver	HCC	methylation	206/7958	364/18723	3.35e-08	7.53e-07	206
GO:00064792	Liver	HCC	protein methylation	111/7958	181/18723	2.36e-07	4.18e-06	111
GO:00082132	Liver	HCC	protein alkylation	111/7958	181/18723	2.36e-07	4.18e-06	111
GO:00165712	Liver	HCC	histone methylation	88/7958	141/18723	1.41e-06	2.02e-05	88
GO:19019871	Liver	HCC	regulation of cell cycle phase transition	211/7958	390/18723	2.11e-06	2.89e-05	211
GO:00427702	Liver	HCC	signal transduction in response to DNA damage	103/7958	172/18723	3.05e-06	4.04e-05	103
GO:00000751	Liver	HCC	cell cycle checkpoint	100/7958	169/18723	8.75e-06	1.02e-04	100
GO:0045786	Liver	HCC	negative regulation of cell cycle	204/7958	385/18723	1.84e-05	1.99e-04	204
GO:00349681	Liver	HCC	histone lysine methylation	70/7958	115/18723	5.32e-05	5.04e-04	70
GO:00000771	Liver	HCC	DNA damage checkpoint	68/7958	115/18723	2.33e-04	1.77e-03	68
GO:0031570	Liver	HCC	DNA integrity checkpoint	71/7958	123/18723	4.64e-04	3.08e-03	71
GO:1901988	Liver	HCC	negative regulation of cell cycle phase transition	132/7958	249/18723	4.97e-04	3.25e-03	132
GO:00180221	Liver	HCC	peptidyl-lysine methylation	74/7958	131/18723	8.46e-04	5.06e-03	74
GO:0010948	Liver	HCC	negative regulation of cell cycle process	152/7958	294/18723	8.50e-04	5.08e-03	152
GO:00322001	Liver	HCC	telomere organization	86/7958	159/18723	2.06e-03	1.04e-02	86
GO:005110112	Liver	HCC	regulation of DNA binding	64/7958	118/18723	6.60e-03	2.68e-02	64

Page: 1

Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0031041	Liver	HCC	Lysine degradation	47/4020	63/8465	1.02e-05	7.58e-05	4.22e-05	47
hsa0031051	Liver	HCC	Lysine degradation	47/4020	63/8465	1.02e-05	7.58e-05	4.22e-05	47

Page: 1

Top

Cell-cell communication analysis

Identification of potential cell-cell interactions between two cell types and their ligand-receptor pairs for different disease states

Ligand

Receptor

LRpair

Pathway

Tissue

Disease Stage

Page: 1

Top

Single-cell gene regulatory network inference analysis

Find out the significant the regulons (TFs) and the target genes of each regulon across cell types for different disease states

Cell Type

Tissue

Disease Stage

Target Gene

RSS

Regulon Activity

∗The dot plots of a searched regulon are shown for all cell subpopulations in each disease state of each tissue based on the regulon specific score inferred using pySCENIC and by calculating the average expression.

Page: 1

Top

Somatic mutation of malignant transformation related genes

Annotation of somatic variants for genes involved in malignant transformation

Hugo Symbol

Variant Class

Variant Classification

dbSNP RS

HGVSc

HGVSp

HGVSp Short

SWISSPROT

BIOTYPE

SIFT

PolyPhen

Tumor Sample Barcode

Tissue

Histology

Sex

Age

Stage

Therapy Types

Drugs

Outcome

DOT1L

SNV

Missense_Mutation

c.736N>A

p.Gly246Ser

p.G246S

Q8TEK3

protein_coding

deleterious(0.03)

probably_damaging(1)

TCGA-BH-A0EE-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

docetaxel

DOT1L

SNV

Missense_Mutation

rs779433641

c.1609C>G

p.Gln537Glu

p.Q537E

Q8TEK3

protein_coding

tolerated(0.08)

benign(0.009)

TCGA-E2-A15K-06

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

DOT1L

SNV

Missense_Mutation

c.186N>A

p.Asp62Glu

p.D62E

Q8TEK3

protein_coding

deleterious(0.03)

possibly_damaging(0.875)

TCGA-EW-A1IZ-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

taxotere

DOT1L

SNV

Missense_Mutation

c.3574G>A

p.Glu1192Lys

p.E1192K

Q8TEK3

protein_coding

deleterious_low_confidence(0.01)

probably_damaging(0.991)

TCGA-GM-A2D9-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

DOT1L

deletion

Frame_Shift_Del

novel

c.354delN

p.Val119Ter

p.V119*

Q8TEK3

protein_coding

TCGA-EW-A2FV-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

docetaxel

DOT1L

SNV

Missense_Mutation

c.4227G>T

p.Lys1409Asn

p.K1409N

Q8TEK3

protein_coding

deleterious_low_confidence(0)

possibly_damaging(0.553)

TCGA-C5-A2LX-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

DOT1L

SNV

Missense_Mutation

novel

c.2884N>T

p.Pro962Ser

p.P962S

Q8TEK3

protein_coding

tolerated_low_confidence(0.15)

benign(0.007)

TCGA-DS-A1OB-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

carboplatin

DOT1L

SNV

Missense_Mutation

novel

c.3023N>G

p.Ser1008Cys

p.S1008C

Q8TEK3

protein_coding

deleterious_low_confidence(0)

possibly_damaging(0.465)

TCGA-DS-A1OB-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

carboplatin

DOT1L

SNV

Missense_Mutation

c.3603N>C

p.Glu1201Asp

p.E1201D

Q8TEK3

protein_coding

deleterious_low_confidence(0)

benign(0.167)

TCGA-FU-A2QG-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

DOT1L

SNV

Missense_Mutation

novel

c.3997G>A

p.Asp1333Asn

p.D1333N

Q8TEK3

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.993)

TCGA-JW-A5VL-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

Page: 1 2 3 4 5 6 7 8 9 10 11

Top

Related drugs of malignant transformation related genes

Identification of chemicals and drugs interact with genes involved in malignant transfromation

(DGIdb 4.0)

Entrez ID	Symbol	Category	Interaction Types	Drug Claim Name	Drug Name	PMIDs
84444	DOT1L	CLINICALLY ACTIONABLE, DNA REPAIR, METHYL TRANSFERASE, DRUGGABLE GENOME, ENZYME	inhibitor	178103597
84444	DOT1L	CLINICALLY ACTIONABLE, DNA REPAIR, METHYL TRANSFERASE, DRUGGABLE GENOME, ENZYME		candesartan	CANDESARTAN	31327267
84444	DOT1L	CLINICALLY ACTIONABLE, DNA REPAIR, METHYL TRANSFERASE, DRUGGABLE GENOME, ENZYME	inhibitor	178103949
84444	DOT1L	CLINICALLY ACTIONABLE, DNA REPAIR, METHYL TRANSFERASE, DRUGGABLE GENOME, ENZYME	inhibitor	178103598	PINOMETOSTAT
84444	DOT1L	CLINICALLY ACTIONABLE, DNA REPAIR, METHYL TRANSFERASE, DRUGGABLE GENOME, ENZYME	inhibitor	315661281
84444	DOT1L	CLINICALLY ACTIONABLE, DNA REPAIR, METHYL TRANSFERASE, DRUGGABLE GENOME, ENZYME	inhibitor	178103599
84444	DOT1L	CLINICALLY ACTIONABLE, DNA REPAIR, METHYL TRANSFERASE, DRUGGABLE GENOME, ENZYME		hydrochlorothiazide	HYDROCHLOROTHIAZIDE	22440088

Page: 1