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: TERT

Gene summary for TERT

Gene summary.

Gene information	Species	Human
	Gene symbol	TERT
	Gene ID	7015
	Gene name	telomerase reverse transcriptase
	Gene Alias	CMM9
	Cytomap	5p15.33
	Gene Type	protein-coding
	GO ID	GO:0000082
	UniProtAcc	O14746

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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
7015	TERT	RNA-P6T2-P6T2-1	Human	Lung	IAC	3.58e-26	7.62e-01	-0.0166
7015	TERT	RNA-P6T2-P6T2-2	Human	Lung	IAC	2.45e-28	7.66e-01	-0.0132
7015	TERT	RNA-P6T2-P6T2-3	Human	Lung	IAC	6.10e-27	7.19e-01	-0.013
7015	TERT	RNA-P6T2-P6T2-4	Human	Lung	IAC	9.48e-21	6.37e-01	-0.0121

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Lung		AAH: Atypical adenomatous hyperplasia
		AIS: Adenocarcinoma in situ
		IAC: Invasive lung adenocarcinoma
		MIA: Minimally invasive adenocarcinoma

∗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:20012338	Lung	IAC	regulation of apoptotic signaling pathway	82/2061	356/18723	4.85e-11	1.44e-08	82
GO:00160556	Lung	IAC	Wnt signaling pathway	95/2061	444/18723	1.13e-10	2.80e-08	95
GO:01987386	Lung	IAC	cell-cell signaling by wnt	95/2061	446/18723	1.46e-10	3.48e-08	95
GO:00301116	Lung	IAC	regulation of Wnt signaling pathway	74/2061	328/18723	1.14e-09	2.05e-07	74
GO:00447723	Lung	IAC	mitotic cell cycle phase transition	85/2061	424/18723	2.69e-08	3.20e-06	85
GO:20012348	Lung	IAC	negative regulation of apoptotic signaling pathway	52/2061	224/18723	1.25e-07	1.11e-05	52
GO:00362947	Lung	IAC	cellular response to decreased oxygen levels	41/2061	161/18723	1.92e-07	1.59e-05	41
GO:00714537	Lung	IAC	cellular response to oxygen levels	43/2061	177/18723	4.03e-07	2.82e-05	43
GO:00316478	Lung	IAC	regulation of protein stability	62/2061	298/18723	5.37e-07	3.32e-05	62
GO:00714564	Lung	IAC	cellular response to hypoxia	38/2061	151/18723	7.33e-07	4.14e-05	38
GO:20012368	Lung	IAC	regulation of extrinsic apoptotic signaling pathway	38/2061	151/18723	7.33e-07	4.14e-05	38
GO:00362938	Lung	IAC	response to decreased oxygen levels	64/2061	322/18723	1.87e-06	8.87e-05	64
GO:00609646	Lung	IAC	regulation of gene silencing by miRNA	18/2061	49/18723	2.10e-06	9.45e-05	18
GO:00616147	Lung	IAC	pri-miRNA transcription by RNA polymerase II	19/2061	55/18723	3.20e-06	1.38e-04	19
GO:00016668	Lung	IAC	response to hypoxia	61/2061	307/18723	3.26e-06	1.39e-04	61
GO:00971918	Lung	IAC	extrinsic apoptotic signaling pathway	47/2061	219/18723	5.11e-06	2.03e-04	47
GO:00351965	Lung	IAC	production of miRNAs involved in gene silencing by miRNA	18/2061	52/18723	5.60e-06	2.13e-04	18
GO:00601475	Lung	IAC	regulation of posttranscriptional gene silencing	18/2061	52/18723	5.60e-06	2.13e-04	18
GO:00000823	Lung	IAC	G1/S transition of mitotic cell cycle	46/2061	214/18723	6.13e-06	2.29e-04	46
GO:00709978	Lung	IAC	neuron death	68/2061	361/18723	6.32e-06	2.32e-04	68

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa051656	Lung	IAC	Human papillomavirus infection	71/1053	331/8465	1.88e-06	7.63e-05	5.06e-05	71
hsa052259	Lung	IAC	Hepatocellular carcinoma	33/1053	168/8465	4.77e-03	2.15e-02	1.43e-02	33
hsa0516511	Lung	IAC	Human papillomavirus infection	71/1053	331/8465	1.88e-06	7.63e-05	5.06e-05	71
hsa0522512	Lung	IAC	Hepatocellular carcinoma	33/1053	168/8465	4.77e-03	2.15e-02	1.43e-02	33

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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

TERT

SNV

Missense_Mutation

c.2929N>C

p.Val977Leu

p.V977L

O14746

protein_coding

tolerated(0.05)

possibly_damaging(0.863)

TCGA-A8-A08F-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

5-fluorouracil

TERT

SNV

Missense_Mutation

c.2633N>A

p.Thr878Asn

p.T878N

O14746

protein_coding

tolerated(0.21)

benign(0.178)

TCGA-D8-A3Z6-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cyclophosphane

TERT

SNV

Missense_Mutation

rs374968697

c.3103N>A

p.Val1035Ile

p.V1035I

O14746

protein_coding

tolerated(1)

benign(0.028)

TCGA-WT-AB41-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxotere

TERT

insertion

Frame_Shift_Ins

novel

c.1704_1705insA

p.Gln569ThrfsTer60

p.Q569Tfs*60

O14746

protein_coding

TCGA-AN-A049-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

TERT

insertion

Frame_Shift_Ins

novel

c.1702_1703insGTCCCGCCCAGGCTGACTGTGGAGGGCT

p.Phe568CysfsTer70

p.F568Cfs*70

O14746

protein_coding

TCGA-AN-A049-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

TERT

deletion

Frame_Shift_Del

novel

c.2465delN

p.Gly822AlafsTer52

p.G822Afs*52

O14746

protein_coding

TCGA-D8-A27V-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

TERT

SNV

Missense_Mutation

novel

c.1562G>A

p.Arg521His

p.R521H

O14746

protein_coding

tolerated(0.07)

benign(0.284)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

TERT

SNV

Missense_Mutation

novel

c.1880N>A

p.Pro627His

p.P627H

O14746

protein_coding

deleterious(0.03)

possibly_damaging(0.808)

TCGA-C5-A7CK-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

TERT

SNV

Missense_Mutation

novel

c.1466N>A

p.Arg489Lys

p.R489K

O14746

protein_coding

tolerated(1)

benign(0.039)

TCGA-EK-A2PI-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Unknown

TERT

SNV

Missense_Mutation

novel

c.1553N>T

p.Ala518Val

p.A518V

O14746

protein_coding

tolerated(0.28)

benign(0.046)

TCGA-MA-AA3Z-01

Cervix

cervical & endocervical cancer

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
7015	TERT	DRUGGABLE GENOME, CLINICALLY ACTIONABLE, ENZYME, RNA DIRECTED DNA POLYMERASE, DRUG RESISTANCE		KML-001
7015	TERT	DRUGGABLE GENOME, CLINICALLY ACTIONABLE, ENZYME, RNA DIRECTED DNA POLYMERASE, DRUG RESISTANCE		TeloB-Vax
7015	TERT	DRUGGABLE GENOME, CLINICALLY ACTIONABLE, ENZYME, RNA DIRECTED DNA POLYMERASE, DRUG RESISTANCE		Dendritic cell vaccine
7015	TERT	DRUGGABLE GENOME, CLINICALLY ACTIONABLE, ENZYME, RNA DIRECTED DNA POLYMERASE, DRUG RESISTANCE		NSC-728558	CHEMBL457246	19167892
7015	TERT	DRUGGABLE GENOME, CLINICALLY ACTIONABLE, ENZYME, RNA DIRECTED DNA POLYMERASE, DRUG RESISTANCE		UO126		28215740
7015	TERT	DRUGGABLE GENOME, CLINICALLY ACTIONABLE, ENZYME, RNA DIRECTED DNA POLYMERASE, DRUG RESISTANCE		Imetelstat	IMETELSTAT
7015	TERT	DRUGGABLE GENOME, CLINICALLY ACTIONABLE, ENZYME, RNA DIRECTED DNA POLYMERASE, DRUG RESISTANCE		RALOXIFENE	RALOXIFENE	15590986
7015	TERT	DRUGGABLE GENOME, CLINICALLY ACTIONABLE, ENZYME, RNA DIRECTED DNA POLYMERASE, DRUG RESISTANCE		OBP-301
7015	TERT	DRUGGABLE GENOME, CLINICALLY ACTIONABLE, ENZYME, RNA DIRECTED DNA POLYMERASE, DRUG RESISTANCE		GRNVAC1
7015	TERT	DRUGGABLE GENOME, CLINICALLY ACTIONABLE, ENZYME, RNA DIRECTED DNA POLYMERASE, DRUG RESISTANCE		Berberine	BERBERINE

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