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: FAM189A2

Gene summary for FAM189A2

Gene summary.

Gene information	Species	Human
	Gene symbol	FAM189A2
	Gene ID	9413
	Gene name	family with sequence similarity 189 member A2
	Gene Alias	C9orf61
	Cytomap	9q21.12
	Gene Type	protein-coding
	GO ID	GO:0008150
	UniProtAcc	Q15884

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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
9413	FAM189A2	AEH-subject3	Human	Endometrium	AEH	1.80e-17	5.17e-01	-0.2576
9413	FAM189A2	AEH-subject5	Human	Endometrium	AEH	2.38e-04	2.79e-01	-0.2953
9413	FAM189A2	EEC-subject1	Human	Endometrium	EEC	6.71e-05	2.77e-01	-0.2682
9413	FAM189A2	GSM6177620_NYU_UCEC1_lib3_lib3	Human	Endometrium	EEC	3.38e-02	-1.55e-01	-0.1883
9413	FAM189A2	GSM6177621_NYU_UCEC2_lib1_lib1	Human	Endometrium	EEC	1.65e-11	3.95e-01	-0.1934
9413	FAM189A2	GSM6177622_NYU_UCEC3_lib1_lib1	Human	Endometrium	EEC	3.29e-02	-1.55e-01	-0.1917
9413	FAM189A2	GSM6177622_NYU_UCEC3_lib2_lib2	Human	Endometrium	EEC	1.03e-03	-1.55e-01	-0.1916
9413	FAM189A2	GSM5252132_BPH389PrGF	Human	Prostate	BPH	7.11e-05	3.05e-01	-0.2247
9413	FAM189A2	GSM5252136_BPH556PrGA1_Fcol	Human	Prostate	BPH	6.98e-04	1.56e-01	-0.23
9413	FAM189A2	GSM5252137_BPH556PrGA2_Fcol	Human	Prostate	BPH	2.10e-05	3.02e-01	-0.23
9413	FAM189A2	048752_1579-all-cells	Human	Prostate	BPH	8.71e-08	3.18e-01	0.1008
9413	FAM189A2	052095_1628-all-cells	Human	Prostate	BPH	3.09e-06	2.18e-01	0.1032
9413	FAM189A2	052097_1595-all-cells	Human	Prostate	BPH	6.41e-04	1.77e-01	0.0972
9413	FAM189A2	052099_1652-all-cells	Human	Prostate	BPH	1.65e-16	3.91e-01	0.1038
9413	FAM189A2	GSM5353222_PA_PB2B_Pool_1_3_S52_L002	Human	Prostate	Tumor	4.13e-05	3.77e-01	0.1608
9413	FAM189A2	GSM5353223_PA_PB2B_Pool_2_S26_L001	Human	Prostate	Tumor	5.45e-09	5.21e-01	0.1604
9413	FAM189A2	GSM5353224_PA_PR5186_Pool_1_2_3_S27_L001	Human	Prostate	Tumor	9.10e-11	5.94e-01	0.1621
9413	FAM189A2	GSM5353227_PA_PR5199-193K_Pool_1_2_3_S55_L002	Human	Prostate	Tumor	1.03e-03	3.84e-01	0.1602
9413	FAM189A2	GSM5353236_PA_PR5251_T1_S7_L001	Human	Prostate	Tumor	3.44e-03	5.56e-01	0.1608
9413	FAM189A2	GSM5353237_PA_PR5251_T2_S8_L001	Human	Prostate	Tumor	2.16e-04	5.84e-01	0.1622

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Endometrium		AEH: Atypical endometrial hyperplasia
Endometrium		EEC: Endometrioid Cancer
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

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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

FAM189A2

SNV

Missense_Mutation

novel

c.416N>T

p.Pro139Leu

p.P139L

Q15884

protein_coding

tolerated(0.09)

benign(0.056)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

FAM189A2

SNV

Missense_Mutation

c.266N>A

p.Ala89Asp

p.A89D

Q15884

protein_coding

deleterious(0)

probably_damaging(0.935)

TCGA-AN-A0FS-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

FAM189A2

SNV

Missense_Mutation

novel

c.238N>T

p.His80Tyr

p.H80Y

Q15884

protein_coding

deleterious(0.02)

probably_damaging(0.932)

TCGA-BH-A0WA-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

FAM189A2

SNV

Missense_Mutation

c.187G>C

p.Asp63His

p.D63H

Q15884

protein_coding

deleterious(0)

possibly_damaging(0.873)

TCGA-C8-A26Y-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

FAM189A2

SNV

Missense_Mutation

novel

c.505C>G

p.Pro169Ala

p.P169A

Q15884

protein_coding

tolerated(0.79)

benign(0.011)

TCGA-S3-AA10-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

cytoxan

FAM189A2

SNV

Missense_Mutation

c.58N>G

p.Leu20Val

p.L20V

Q15884

protein_coding

tolerated(0.14)

probably_damaging(0.998)

TCGA-IR-A3LL-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

FAM189A2

SNV

Missense_Mutation

novel

c.1256C>G

p.Thr419Arg

p.T419R

Q15884

protein_coding

deleterious(0)

benign(0.075)

TCGA-JW-A5VL-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

FAM189A2

SNV

Missense_Mutation

c.385N>A

p.Glu129Lys

p.E129K

Q15884

protein_coding

tolerated(0.14)

benign(0.355)

TCGA-MA-AA41-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

FAM189A2

SNV

Missense_Mutation

novel

c.715N>A

p.Pro239Thr

p.P239T

Q15884

protein_coding

tolerated(0.11)

benign(0.003)

TCGA-VS-A9UP-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

FAM189A2

SNV

Missense_Mutation

rs777160692

c.584C>T

p.Pro195Leu

p.P195L

Q15884

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-XS-A8TJ-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

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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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