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: BCR

Gene summary for BCR

Gene summary.

Gene information	Species	Human
	Gene symbol	BCR
	Gene ID	613
	Gene name	BCR activator of RhoGEF and GTPase
	Gene Alias	ALL
	Cytomap	22q11.23
	Gene Type	protein-coding
	GO ID	GO:0006464
	UniProtAcc	P11274

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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
613	BCR	HTA11_3410_2000001011	Human	Colorectum	AD	4.34e-05	3.87e-01	0.0155
613	BCR	HTA11_1938_2000001011	Human	Colorectum	AD	1.40e-08	8.14e-01	-0.0811
613	BCR	HTA11_347_2000001011	Human	Colorectum	AD	1.68e-02	3.19e-01	-0.1954
613	BCR	HTA11_411_2000001011	Human	Colorectum	SER	1.63e-05	1.03e+00	-0.2602
613	BCR	HTA11_3361_2000001011	Human	Colorectum	AD	3.25e-05	6.01e-01	-0.1207
613	BCR	HTA11_83_2000001011	Human	Colorectum	SER	2.63e-06	7.65e-01	-0.1526
613	BCR	HTA11_696_2000001011	Human	Colorectum	AD	1.49e-25	1.02e+00	-0.1464
613	BCR	HTA11_866_2000001011	Human	Colorectum	AD	7.28e-03	3.74e-01	-0.1001
613	BCR	HTA11_1391_2000001011	Human	Colorectum	AD	2.13e-04	5.44e-01	-0.059
613	BCR	HTA11_2992_2000001011	Human	Colorectum	SER	1.30e-07	1.03e+00	-0.1706
613	BCR	HTA11_5212_2000001011	Human	Colorectum	AD	6.26e-07	8.79e-01	-0.2061
613	BCR	HTA11_5216_2000001011	Human	Colorectum	SER	1.55e-05	9.51e-01	-0.1462
613	BCR	HTA11_546_2000001011	Human	Colorectum	AD	1.11e-11	1.06e+00	-0.0842
613	BCR	A015-C-203	Human	Colorectum	FAP	3.77e-12	-1.68e-01	-0.1294
613	BCR	A002-C-201	Human	Colorectum	FAP	4.04e-04	-7.30e-02	0.0324
613	BCR	A001-C-119	Human	Colorectum	FAP	2.74e-02	-1.01e-01	-0.1557
613	BCR	A001-C-108	Human	Colorectum	FAP	2.41e-05	-1.36e-01	-0.0272
613	BCR	A002-C-205	Human	Colorectum	FAP	1.67e-09	-2.09e-01	-0.1236
613	BCR	A015-C-006	Human	Colorectum	FAP	1.07e-06	-1.45e-01	-0.0994
613	BCR	A015-C-106	Human	Colorectum	FAP	1.69e-04	-2.11e-01	-0.0511

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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
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:0090630	Colorectum	FAP	activation of GTPase activity	27/2622	115/18723	4.23e-03	2.90e-02	27
GO:00099132	Colorectum	FAP	epidermal cell differentiation	42/2622	202/18723	5.08e-03	3.37e-02	42
GO:00510563	Colorectum	CRC	regulation of small GTPase mediated signal transduction	69/2078	302/18723	3.34e-09	9.08e-07	69
GO:00315894	Colorectum	CRC	cell-substrate adhesion	78/2078	363/18723	6.22e-09	1.49e-06	78
GO:00343294	Colorectum	CRC	cell junction assembly	83/2078	420/18723	1.08e-07	1.29e-05	83
GO:00072653	Colorectum	CRC	Ras protein signal transduction	70/2078	337/18723	1.49e-07	1.66e-05	70
GO:00070444	Colorectum	CRC	cell-substrate junction assembly	29/2078	95/18723	2.34e-07	2.27e-05	29
GO:01501154	Colorectum	CRC	cell-substrate junction organization	30/2078	101/18723	2.85e-07	2.54e-05	30
GO:00430874	Colorectum	CRC	regulation of GTPase activity	69/2078	348/18723	1.11e-06	6.69e-05	69
GO:00480414	Colorectum	CRC	focal adhesion assembly	26/2078	87/18723	1.52e-06	8.15e-05	26
GO:00465782	Colorectum	CRC	regulation of Ras protein signal transduction	43/2078	189/18723	3.26e-06	1.47e-04	43
GO:00071604	Colorectum	CRC	cell-matrix adhesion	50/2078	233/18723	3.28e-06	1.47e-04	50
GO:00435473	Colorectum	CRC	positive regulation of GTPase activity	49/2078	255/18723	8.67e-05	1.77e-03	49
GO:00085442	Colorectum	CRC	epidermis development	57/2078	324/18723	2.88e-04	4.59e-03	57
GO:00467774	Colorectum	CRC	protein autophosphorylation	42/2078	227/18723	6.08e-04	8.10e-03	42
GO:00435881	Colorectum	CRC	skin development	47/2078	263/18723	6.63e-04	8.74e-03	47
GO:00072662	Colorectum	CRC	Rho protein signal transduction	28/2078	137/18723	9.97e-04	1.19e-02	28
GO:0050804	Colorectum	CRC	modulation of chemical synaptic transmission	70/2078	439/18723	1.15e-03	1.33e-02	70
GO:0099177	Colorectum	CRC	regulation of trans-synaptic signaling	70/2078	440/18723	1.23e-03	1.38e-02	70
GO:00099133	Colorectum	CRC	epidermal cell differentiation	37/2078	202/18723	1.50e-03	1.59e-02	37

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa05220	Colorectum	AD	Chronic myeloid leukemia	31/2092	76/8465	1.41e-03	8.46e-03	5.39e-03	31
hsa052201	Colorectum	AD	Chronic myeloid leukemia	31/2092	76/8465	1.41e-03	8.46e-03	5.39e-03	31
hsa052204	Colorectum	FAP	Chronic myeloid leukemia	23/1404	76/8465	2.14e-03	1.05e-02	6.39e-03	23
hsa052205	Colorectum	FAP	Chronic myeloid leukemia	23/1404	76/8465	2.14e-03	1.05e-02	6.39e-03	23
hsa052206	Colorectum	CRC	Chronic myeloid leukemia	18/1091	76/8465	6.86e-03	3.37e-02	2.28e-02	18
hsa052207	Colorectum	CRC	Chronic myeloid leukemia	18/1091	76/8465	6.86e-03	3.37e-02	2.28e-02	18
hsa0522021	Liver	HCC	Chronic myeloid leukemia	55/4020	76/8465	8.67e-06	6.91e-05	3.84e-05	55
hsa0522031	Liver	HCC	Chronic myeloid leukemia	55/4020	76/8465	8.67e-06	6.91e-05	3.84e-05	55
hsa0522018	Oral cavity	OSCC	Chronic myeloid leukemia	56/3704	76/8465	1.04e-07	7.43e-07	3.78e-07	56
hsa0522019	Oral cavity	OSCC	Chronic myeloid leukemia	56/3704	76/8465	1.04e-07	7.43e-07	3.78e-07	56
hsa0522025	Oral cavity	LP	Chronic myeloid leukemia	37/2418	76/8465	1.53e-04	9.08e-04	5.86e-04	37
hsa0522035	Oral cavity	LP	Chronic myeloid leukemia	37/2418	76/8465	1.53e-04	9.08e-04	5.86e-04	37

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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

BCR

SNV

Missense_Mutation

c.900G>C

p.Gln300His

p.Q300H

P11274

protein_coding

tolerated_low_confidence(0.47)

benign(0.275)

TCGA-AN-A0FT-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

BCR

SNV

Missense_Mutation

c.2311N>C

p.Glu771Gln

p.E771Q

P11274

protein_coding

deleterious(0.04)

possibly_damaging(0.688)

TCGA-BH-A209-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

BCR

SNV

Missense_Mutation

novel

c.3671N>C

p.Asn1224Thr

p.N1224T

P11274

protein_coding

tolerated(0.15)

benign(0.001)

TCGA-D8-A1JU-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

BCR

SNV

Missense_Mutation

c.2710N>A

p.Asp904Asn

p.D904N

P11274

protein_coding

deleterious(0.03)

benign(0.41)

TCGA-GM-A2D9-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

BCR

insertion

In_Frame_Ins

novel

c.2067_2068insTTAGTACCAGGAATTAATCTCAGCTCCTTCCCA

p.Asn689_Glu690insLeuValProGlyIleAsnLeuSerSerPhePro

p.N689_E690insLVPGINLSSFP

P11274

protein_coding

TCGA-B6-A0IE-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

BCR

deletion

Frame_Shift_Del

novel

c.2203delC

p.Leu735PhefsTer53

p.L735Ffs*53

P11274

protein_coding

TCGA-D8-A27V-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

BCR

SNV

Missense_Mutation

rs775101020

c.1607N>T

p.Pro536Leu

p.P536L

P11274

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

BCR

SNV

Missense_Mutation

novel

c.3656N>A

p.Ser1219Asn

p.S1219N

P11274

protein_coding

deleterious(0.03)

benign(0.104)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

BCR

SNV

Missense_Mutation

c.1816N>C

p.Glu606Gln

p.E606Q

P11274

protein_coding

tolerated(0.1)

benign(0.217)

TCGA-C5-A1BQ-01

Cervix

cervical & endocervical cancer

Female

>=65

III/IV

Chemotherapy

cisplatin

BCR

SNV

Missense_Mutation

c.1816N>C

p.Glu606Gln

p.E606Q

P11274

protein_coding

tolerated(0.1)

benign(0.217)

TCGA-C5-A3HL-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
613	BCR	TUMOR SUPPRESSOR, SERINE THREONINE KINASE, TYROSINE KINASE, CLINICALLY ACTIONABLE, KINASE, ENZYME, DRUGGABLE GENOME		ponatinib	PONATINIB
613	BCR	TUMOR SUPPRESSOR, SERINE THREONINE KINASE, TYROSINE KINASE, CLINICALLY ACTIONABLE, KINASE, ENZYME, DRUGGABLE GENOME		Nilotinib	NILOTINIB
613	BCR	TUMOR SUPPRESSOR, SERINE THREONINE KINASE, TYROSINE KINASE, CLINICALLY ACTIONABLE, KINASE, ENZYME, DRUGGABLE GENOME		Ponatinib	PONATINIB
613	BCR	TUMOR SUPPRESSOR, SERINE THREONINE KINASE, TYROSINE KINASE, CLINICALLY ACTIONABLE, KINASE, ENZYME, DRUGGABLE GENOME		nilotinib	NILOTINIB
613	BCR	TUMOR SUPPRESSOR, SERINE THREONINE KINASE, TYROSINE KINASE, CLINICALLY ACTIONABLE, KINASE, ENZYME, DRUGGABLE GENOME		IMATINIB	IMATINIB	22148584,24681986
613	BCR	TUMOR SUPPRESSOR, SERINE THREONINE KINASE, TYROSINE KINASE, CLINICALLY ACTIONABLE, KINASE, ENZYME, DRUGGABLE GENOME		Imatinib	IMATINIB
613	BCR	TUMOR SUPPRESSOR, SERINE THREONINE KINASE, TYROSINE KINASE, CLINICALLY ACTIONABLE, KINASE, ENZYME, DRUGGABLE GENOME		busulfan	BUSULFAN
613	BCR	TUMOR SUPPRESSOR, SERINE THREONINE KINASE, TYROSINE KINASE, CLINICALLY ACTIONABLE, KINASE, ENZYME, DRUGGABLE GENOME		Bosutinib	BOSUTINIB
613	BCR	TUMOR SUPPRESSOR, SERINE THREONINE KINASE, TYROSINE KINASE, CLINICALLY ACTIONABLE, KINASE, ENZYME, DRUGGABLE GENOME		GNF-2	CHEMBL483847	16415863
613	BCR	TUMOR SUPPRESSOR, SERINE THREONINE KINASE, TYROSINE KINASE, CLINICALLY ACTIONABLE, KINASE, ENZYME, DRUGGABLE GENOME		vincristine	VINCRISTINE

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