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

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	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: MLLT6

Gene summary for MLLT6

Gene summary.

Gene information	Species	Human
	Gene symbol	MLLT6
	Gene ID	4302
	Gene name	MLLT6, PHD finger containing
	Gene Alias	AF17
	Cytomap	17q12
	Gene Type	protein-coding
	GO ID	GO:0002028
	UniProtAcc	A0A087WW39

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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
4302	MLLT6	P31T-E	Human	Esophagus	ESCC	1.81e-19	8.88e-02	0.1251
4302	MLLT6	P32T-E	Human	Esophagus	ESCC	6.53e-13	2.33e-02	0.1666
4302	MLLT6	P36T-E	Human	Esophagus	ESCC	2.44e-09	2.06e-01	0.1187
4302	MLLT6	P37T-E	Human	Esophagus	ESCC	1.27e-08	7.75e-02	0.1371
4302	MLLT6	P39T-E	Human	Esophagus	ESCC	3.19e-15	7.85e-03	0.0894
4302	MLLT6	P40T-E	Human	Esophagus	ESCC	1.61e-06	4.85e-02	0.109
4302	MLLT6	P42T-E	Human	Esophagus	ESCC	2.15e-13	1.36e-01	0.1175
4302	MLLT6	P44T-E	Human	Esophagus	ESCC	4.71e-07	-1.91e-02	0.1096
4302	MLLT6	P47T-E	Human	Esophagus	ESCC	5.95e-18	2.42e-02	0.1067
4302	MLLT6	P48T-E	Human	Esophagus	ESCC	4.81e-09	2.16e-01	0.0959
4302	MLLT6	P52T-E	Human	Esophagus	ESCC	6.47e-22	7.01e-02	0.1555
4302	MLLT6	P54T-E	Human	Esophagus	ESCC	1.42e-09	1.64e-01	0.0975
4302	MLLT6	P56T-E	Human	Esophagus	ESCC	4.62e-07	5.53e-01	0.1613
4302	MLLT6	P57T-E	Human	Esophagus	ESCC	1.38e-20	2.58e-01	0.0926
4302	MLLT6	P61T-E	Human	Esophagus	ESCC	7.82e-13	1.83e-01	0.099
4302	MLLT6	P62T-E	Human	Esophagus	ESCC	1.05e-23	2.62e-01	0.1302
4302	MLLT6	P65T-E	Human	Esophagus	ESCC	1.55e-16	1.16e-01	0.0978
4302	MLLT6	P74T-E	Human	Esophagus	ESCC	1.14e-09	1.65e-01	0.1479
4302	MLLT6	P75T-E	Human	Esophagus	ESCC	3.37e-16	6.17e-02	0.1125
4302	MLLT6	P76T-E	Human	Esophagus	ESCC	2.79e-12	1.30e-01	0.1207

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Breast		IDC: Invasive ductal carcinoma
		DCIS: Ductal carcinoma in situ
		Precancer(BRCA1-mut): Precancerous lesion from BRCA1 mutation carriers
Colorectum (GSE201348)		FAP: Familial adenomatous polyposis
		CRC: Colorectal cancer
Colorectum (HTA11)		AD: Adenomas
		SER: Sessile serrated lesions
		MSI-H: Microsatellite-high colorectal cancer
		MSS: Microsatellite stable colorectal cancer
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias
Liver		HCC: Hepatocellular carcinoma
		NAFLD: Non-alcoholic fatty liver disease
Oral Cavity		EOLP: Erosive Oral lichen planus
		LP: leukoplakia
		NEOLP: Non-erosive oral lichen planus
		OSCC: Oral squamous cell carcinoma
Prostate		BPH: Benign Prostatic Hyperplasia
Thyroid		ATC: Anaplastic thyroid cancer
		HT: Hashimoto's thyroiditis
		PTC: Papillary thyroid cancer

∗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.

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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).

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Enriched GO biological processes.

GO ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	Count
GO:005087813	Breast	IDC	regulation of body fluid levels	50/1434	379/18723	1.12e-04	2.10e-03	50
GO:001095913	Breast	IDC	regulation of metal ion transport	52/1434	406/18723	1.76e-04	2.97e-03	52
GO:00432703	Breast	IDC	positive regulation of ion transport	36/1434	275/18723	1.11e-03	1.22e-02	36
GO:005087823	Breast	DCIS	regulation of body fluid levels	50/1390	379/18723	5.17e-05	1.06e-03	50
GO:001095921	Breast	DCIS	regulation of metal ion transport	50/1390	406/18723	2.86e-04	4.22e-03	50
GO:004327011	Breast	DCIS	positive regulation of ion transport	34/1390	275/18723	2.35e-03	2.13e-02	34
GO:00030144	Breast	DCIS	renal system process	16/1390	110/18723	7.16e-03	4.85e-02	16
GO:0002028	Colorectum	AD	regulation of sodium ion transport	36/3918	90/18723	2.89e-05	5.37e-04	36
GO:0010765	Colorectum	AD	positive regulation of sodium ion transport	17/3918	35/18723	2.48e-04	3.13e-03	17
GO:0050878	Colorectum	AD	regulation of body fluid levels	108/3918	379/18723	2.54e-04	3.20e-03	108
GO:0003014	Colorectum	AD	renal system process	35/3918	110/18723	4.85e-03	3.27e-02	35
GO:0055067	Colorectum	AD	monovalent inorganic cation homeostasis	45/3918	151/18723	6.19e-03	3.88e-02	45
GO:0031056	Colorectum	AD	regulation of histone modification	45/3918	152/18723	7.05e-03	4.31e-02	45
GO:00020282	Colorectum	MSS	regulation of sodium ion transport	32/3467	90/18723	9.56e-05	1.50e-03	32
GO:00508782	Colorectum	MSS	regulation of body fluid levels	99/3467	379/18723	1.40e-04	2.07e-03	99
GO:00107652	Colorectum	MSS	positive regulation of sodium ion transport	15/3467	35/18723	7.59e-04	8.09e-03	15
GO:0016570	Colorectum	MSS	histone modification	113/3467	463/18723	8.37e-04	8.68e-03	113
GO:00310562	Colorectum	MSS	regulation of histone modification	41/3467	152/18723	6.41e-03	4.27e-02	41
GO:00020284	Colorectum	FAP	regulation of sodium ion transport	33/2622	90/18723	6.51e-08	4.54e-06	33
GO:00107654	Colorectum	FAP	positive regulation of sodium ion transport	16/2622	35/18723	5.99e-06	1.90e-04	16

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Enriched KEGG pathways.

Pathway ID

Tissue

Disease Stage

Description

Gene Ratio

Bg Ratio

pvalue

p.adjust

qvalue

Count

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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

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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.

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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

MLLT6

SNV

Missense_Mutation

novel

c.877N>A

p.Glu293Lys

p.E293K

protein_coding

tolerated(0.08)

probably_damaging(0.953)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

MLLT6

insertion

Frame_Shift_Ins

novel

c.997_998insGTAAAGA

p.Ser333CysfsTer24

p.S333Cfs*24

protein_coding

TCGA-AQ-A04J-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

MLLT6

insertion

Frame_Shift_Ins

novel

c.998_999insACTGACACTTATCGACGTTGAGA

p.Ser334LeufsTer123

p.S334Lfs*123

protein_coding

TCGA-AQ-A04J-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

MLLT6

deletion

Frame_Shift_Del

novel

c.609_619delCAGCATGGGGG

p.Ser204ArgfsTer42

p.S204Rfs*42

protein_coding

TCGA-B6-A409-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cyclophosphamide

MLLT6

deletion

Frame_Shift_Del

novel

c.1382_1392delNNNNNNNNNNN

p.Thr461ArgfsTer92

p.T461Rfs*92

protein_coding

TCGA-C8-A12V-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

MLLT6

SNV

Missense_Mutation

novel

c.235N>C

p.Asp79His

p.D79H

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-EK-A2PL-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Unknown

MLLT6

SNV

Missense_Mutation

novel

c.228N>C

p.Lys76Asn

p.K76N

protein_coding

deleterious(0)

probably_damaging(0.997)

TCGA-HM-A4S6-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Chemotherapy

cisplatin

MLLT6

SNV

Missense_Mutation

novel

c.1831C>G

p.Gln611Glu

p.Q611E

protein_coding

deleterious(0)

probably_damaging(0.939)

TCGA-IR-A3LK-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Chemotherapy

cisplatin

MLLT6

SNV

Missense_Mutation

novel

c.1927N>A

p.Glu643Lys

p.E643K

protein_coding

deleterious(0)

probably_damaging(0.99)

TCGA-MY-A5BF-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Chemotherapy

cisplatin

MLLT6

SNV

Missense_Mutation

novel

c.1330N>T

p.Arg444Trp

p.R444W

protein_coding

deleterious(0)

probably_damaging(0.997)

TCGA-AA-3492-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

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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

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