Cancer Cell Metabolism Database ~~ Bioinformatics and Systems Medicine Laboratory ~~

Cancer Cell Metabolism Gene Database

Cancer Cell Metabolism Gene DB

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	Gene Summary
	Phenotypic Information (metabolism pathway, cancer, disease, phenome)
	Mutations : SVs, CNVs, SNVs
	Gene expression: GE, Protein, DEGE, CNV vs GE
	Gene-Gene Network Information: Co-Expression Network, Interacting Genes & KEGG
	Pharmacological Information: Drug-Gene Network
	Cross referenced IDs

Gene Summary for STK11

Basic gene info.	Gene symbol	STK11
	Gene name	serine/threonine kinase 11
	Synonyms	LKB1\|PJS\|hLKB1
	Cytomap	UCSC genome browser: 19p13.3
	Genomic location	chr19 :1205797-1228434
	Type of gene	protein-coding
	RefGenes	NM_000455.4,
	Ensembl id	ENSG00000118046
	Description	liver kinase B1polarization-related protein LKB1renal carcinoma antigen NY-REN-19serine/threonine-protein kinase 11serine/threonine-protein kinase LKB1serine/threonine-protein kinase STK11
	Modification date	20141222
dbXrefs	MIM : 602216
	HGNC : HGNC
	Ensembl : ENSG00000118046
	HPRD : 03740
Protein	UniProt: Q15831 go to UniProt's Cross Reference DB Table
Expression	CleanEX: HS_STK11
	BioGPS: 6794
	Gene Expression Atlas: ENSG00000118046
	The Human Protein Atlas: ENSG00000118046
Pathway	NCI Pathway Interaction Database: STK11
	KEGG: STK11
	REACTOME: STK11
	ConsensusPathDB
	Pathway Commons: STK11
Metabolism	MetaCyc: STK11
	HUMANCyc: STK11
Regulation	Ensembl's Regulation: ENSG00000118046
	miRBase: chr19 :1,205,797-1,228,434
	TargetScan: NM_000455
	cisRED: ENSG00000118046
Context	iHOP: STK11
	cancer metabolism search in PubMed: STK11
	UCL Cancer Institute: STK11
Assigned class in ccmGDB	A - This gene has a literature evidence and it belongs to cancer gene.
References showing role of STK11 in cancer cell metabolism	1. Shackelford DB, Abt E, Gerken L, Vasquez DS, Seki A, et al. (2013) LKB1 inactivation dictates therapeutic response of non-small cell lung cancer to the metabolism drug phenformin. Cancer cell 23: 143-158. go to article 2. Liu Y, Marks K, Cowley GS, Carretero J, Liu Q, et al. (2013) Metabolic and functional genomic studies identify deoxythymidylate kinase as a target in LKB1-mutant lung cancer. Cancer discovery 3: 870-879. go to article 3. Dupuy F, Griss T, Blagih J, Bridon G, Avizonis D, et al. (2013) LKB1 is a central regulator of tumor initiation and pro-growth metabolism in ErbB2-mediated breast cancer. Cancer Metab 1: 18. go to article

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Phenotypic Information for STK11(metabolism pathway, cancer, disease, phenome)

Cancer Description
Cancer	CGAP: STK11
	Familial Cancer Database: STK11

* This gene is included in those cancer gene databases.


Oncogene ¹	Tumor Suppressor gene ²	Cancer Gene Census ³	CancerGenes ⁴	Network of Cancer Gene ⁵	Significant driver gene in LUAD ⁶,	Therapeutic Vulnerabilities in Cancer⁷

cf) number; DB name
1 Oncogene; http://nar.oxfordjournals.org/content/35/suppl_1/D721.long,
2 Tumor Suppressor gene; https://bioinfo.uth.edu/TSGene/,
3 Cancer Gene Census; http://www.nature.com/nrc/journal/v4/n3/abs/nrc1299.html,
4 CancerGenes; http://nar.oxfordjournals.org/content/35/suppl_1/D721.long,
5 Network of Cancer Gene; http://ncg.kcl.ac.uk/index.php,
6 http://www.sciencedirect.com/science/article/pii/S0092867412010227,
7Therapeutic Vulnerabilities in Cancer; http://cbio.mskcc.org/cancergenomics/statius/

Metabolic Pathway Description
REACTOME_INTEGRATION_OF_ENERGY_METABOLISM

Others
OMIM	175200; phenotype. 273300; phenotype. 602216; gene.
Orphanet	2869; Peutz-Jeghers syndrome.
Disease	KEGG Disease: STK11
	MedGen: STK11 (Human Medical Genetics with Condition)
	ClinVar: STK11
Phenotype	MGI: STK11 (International Mouse Phenotyping Consortium)
Phenotype	PhenomicDB: STK11

Mutations for STK11

* Under tables are showing count per each tissue to give us broad intuition about tissue specific mutation patterns.You can go to the detailed page for each mutation database's web site.

Structural Variants in COSMIC : go to COSMIC mutation histogram

- Statistics for Tissue and Mutation type

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- For Inter-chromosomal Variations

There's no inter-chromosomal structural variation.

- For Intra-chromosomal Variations

* Intra-chromosomal variantions includes 'intrachromosomal amplicon to amplicon', 'intrachromosomal amplicon to non-amplified dna', 'intrachromosomal deletion', 'intrachromosomal fold-back inversion', 'intrachromosomal inversion', 'intrachromosomal tandem duplication', 'Intrachromosomal unknown type', 'intrachromosomal with inverted orientation', 'intrachromosomal with non-inverted orientation'.

Sample	Symbol_a	Chr_a	Start_a	End_a	Symbol_b	Chr_b	Start_b	End_b
ovary	STK11	chr19	1213436	1213456	MED16	chr19	870704	870724
ovary	STK11	chr19	1215366	1215386	STK11	chr19	1223894	1223914
ovary	STK11	chr19	1224761	1224781	SBNO2	chr19	1138520	1138540

cf) Tissue number; Tissue name (1;Breast, 2;Central_nervous_system, 3;Haematopoietic_and_lymphoid_tissue, 4;Large_intestine, 5;Liver, 6;Lung, 7;Ovary, 8;Pancreas, 9;Prostate, 10;Skin, 11;Soft_tissue, 12;Upper_aerodigestive_tract)

Related fusion transcripts : go to Chitars2.0

* From mRNA Sanger sequences, Chitars2.0 arranged chimeric transcripts. This table shows STK11 related fusion information.

ID	Head Gene						Tail Gene
Accession	Gene_a	qStart_a	qEnd_a	Chromosome_a	tStart_a	tEnd_a	Gene_a	qStart_a	qEnd_a	Chromosome_a	tStart_a	tEnd_a
AI968661	RPP14	1	195	3	58305165	58305359	STK11	190	312	19	1224618	1224740
AI365374	RPP14	1	195	3	58305165	58305359	STK11	190	446	19	1224484	1224740

Other DBs for Structural Variants

Structural Variants in Ensembl: go to Ensembl Structural variation

Structural Variants in dbVar: go to dbVar

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Copy Number Variations in COSMIC : go to COSMIC mutation CNV/Expr

Mutation type/ Tissue ID

brca

cns

cerv

endome

haematopo

kidn

Lintest

liver

lung

ovary

pancre

prost

skin

stoma

thyro

urina

Total # sample

GAIN (# sample)

LOSS (# sample)

cf) Tissue ID; Tissue type (1; Breast, 2; Central_nervous_system, 3; Cervix, 4; Endometrium, 5; Haematopoietic_and_lymphoid_tissue, 6; Kidney, 7; Large_intestine, 8; Liver, 9; Lung, 10; NS, 11; Ovary, 12; Pancreas, 13; Prostate, 14; Skin, 15; Stomach, 16; Thyroid, 17; Urinary_tract)

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SNV Counts per Each Loci in COSMIC data : go to COSMIC point mutation

: Non-synonymous mutation, : Synonymous mutation, Circle size denotes number of samples.
Maximum mutation count=35

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Somatic Mutation Counts per Tissue in COSMIC data

Stat. for Non-Synonymous SNVs (# total SNVs=236)	Stat. for Synonymous SNVs (# total SNVs=32)

Stat. for Deletions (# total SNVs=60)	Stat. for Insertions (# total SNVs=15)

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Top 10 SNVs Having the Most Samples in COSMIC data

* When you move the cursor on each content, you can see more deailed mutation information on the Tooltip. Those are primary_site,primary_histology,mutation(aa),pubmedID.

GRCh37 position	Mutation(aa)	Unique sampleID count
chr19:1223125-1223125	p.F354L	29
chr19:1221319-1221319	p.P281L	17
chr19:1206913-1226646	p.0?	16
chr19:1207021-1207021	p.Q37*	12
chr19:1220487-1220487	p.D194Y	9
chr19:1220415-1220415	p.Q170*	8
chr19:1207092-1207092	p.Y60Y	7
chr19:1226570-1226570	p.R409Q	6
chr19:1221210-1221210	p.?	6
chr19:1207120-1207120	p.E70*	4

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SNV Counts per Each Loci in TCGA data

: non-synonymous mutation, : synonymous mutation, Circle size denotes number of samples.
maximum mutation count=5

Point Mutation/ Tissue ID	1	2	3	4	5	6	7	8	9	10	11	12	13	14	15	16	17	18	19	20
# sample			1	34			1		3	1		12	1				3	2		1
# mutation			1	37			2		2	1		13	1				3	2		1
nonsynonymous SNV				22			2		1	1		13					2	1		1
synonymous SNV			1	15					1				1				1	1

cf) Tissue ID; Tissue type (1; BLCA[Bladder Urothelial Carcinoma], 2; BRCA[Breast invasive carcinoma], 3; CESC[Cervical squamous cell carcinoma and endocervical adenocarcinoma], 4; COAD[Colon adenocarcinoma], 5; GBM[Glioblastoma multiforme], 6; Glioma Low Grade, 7; HNSC[Head and Neck squamous cell carcinoma], 8; KICH[Kidney Chromophobe], 9; KIRC[Kidney renal clear cell carcinoma], 10; KIRP[Kidney renal papillary cell carcinoma], 11; LAML[Acute Myeloid Leukemia], 12; LUAD[Lung adenocarcinoma], 13; LUSC[Lung squamous cell carcinoma], 14; OV[Ovarian serous cystadenocarcinoma ], 15; PAAD[Pancreatic adenocarcinoma], 16; PRAD[Prostate adenocarcinoma], 17; SKCM[Skin Cutaneous Melanoma], 18:STAD[Stomach adenocarcinoma], 19:THCA[Thyroid carcinoma], 20:UCEC[Uterine Corpus Endometrial Carcinoma])

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Top 10 SNVs Having the Most Samples in TCGA data

* We represented just top 10 SNVs. When you move the cursor on each content, you can see more deailed mutation information on the Tooltip. Those are primary_site, primary_histology, mutation(aa), pubmedID.

Genomic Position	Mutation(aa)	Unique sampleID count
chr19:1226570	p.R409Q	5
chr19:1219403	p.Q152R	3
chr19:1220416	p.Y60Y	2
chr19:1207092	p.Q170R	2
chr19:1220429	p.H174H	2
chr19:1207078	p.G56W	2
chr19:1207080	p.Y60C	1
chr19:1220487	p.Q152K	1
chr19:1207152	p.S216F	1
chr19:1221279	p.D350D	1

Other DBs for Point Mutations

Point Mutation Table of Ensembl: go to Ensembl variation table

Mutation of cBioPortal: go to cBioPortal's Cross-cancer alteration summary

Copy Number for STK11 in TCGA

* Copy number data were extracted from TCGA using R package TCGA-Assembler. The URLs of all public data files on TCGA DCC data server were gathered on Jan-05-2015. Function ProcessCNAData in TCGA-Assembler package was used to obtain gene-level copy number value which is calculated as the average copy number of the genomic region of a gene.

cf) Tissue ID[Tissue type]: BLCA[Bladder Urothelial Carcinoma], BRCA[Breast invasive carcinoma], CESC[Cervical squamous cell carcinoma and endocervical adenocarcinoma], COAD[Colon adenocarcinoma], GBM[Glioblastoma multiforme], Glioma Low Grade, HNSC[Head and Neck squamous cell carcinoma], KICH[Kidney Chromophobe], KIRC[Kidney renal clear cell carcinoma], KIRP[Kidney renal papillary cell carcinoma], LAML[Acute Myeloid Leukemia], LUAD[Lung adenocarcinoma], LUSC[Lung squamous cell carcinoma], OV[Ovarian serous cystadenocarcinoma ], PAAD[Pancreatic adenocarcinoma], PRAD[Prostate adenocarcinoma], SKCM[Skin Cutaneous Melanoma], STAD[Stomach adenocarcinoma], THCA[Thyroid carcinoma], UCEC[Uterine Corpus Endometrial Carcinoma]

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Gene Expression for STK11

Gene Expression in Cancer Cell-lines (CCLE)

* CCLE gene expression data were extracted from CCLE_Expression_Entrez_2012-10-18.res: Gene-centric RMA-normalized mRNA expression data.

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Protein Expression Plot (RPPA)

*RPPA protein expression data were extracted from TCPA (The Cancer Proteome Atlas). Normalized data based on replicated based normalization (RBN) was used to draw following figures.

Differential Gene Expression in Primary Tumors (TCGA)

* Normalized gene expression data of RNASeqV2 was extracted from TCGA using R package TCGA-Assembler. The URLs of all public data files on TCGA DCC data server were gathered at Jan-05-2015. Only eight cancer types have enough normal control samples for differential expression analysis.
(t test, adjusted p<0.05 (using Benjamini-Hochberg FDR))

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CNV vs Gene Expression Plot

* This plots show the correlation between CNV and gene expression.

: Open all plots for all cancer types

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Gene-Gene Network Information

Co-Expressed gene's network Plot

* Co-Expression network figures were drawn using R package igraph. Only the top 20 genes with the highest correlations were shown.
Red circle: input gene, orange circle: cell metabolism gene, sky circle: other gene

: Open all plots for all cancer types


ADAT3,BTBD2,TPGS1,C19orf25,CACTIN,TMEM259,CSNK1G2, ABHD17A,HDGFRP2,KLF16,MBD3,MED16,MIER2,NDUFS7, POLR2E,POLRMT,RNF126,SIRT6,SPPL2B,STK11,WDR18	ABCF3,ACTR1B,ATP5D,RABL6,CTBP1,EVI5L,CPTP, HSF1,KEAP1,LONP1,MAP2K2,NTMT1,MIB2,MRPL12, NDUFV1,NOSIP,POLRMT,PTGES2,SIVA1,STK11,TIMM44

ADAT3,CACTIN,TMEM259,CSNK1G2,DOHH,FZR1,HDGFRP2, CAMSAP3,MAP2K2,NR2F6,POLRMT,RAVER1,REXO1,RNF126, SAMD1,SF3A2,SPPL2B,STK11,TCF3,XAB2,ZNF414	ADAT3,VPS51___IFT46,CC2D1A,CCDC61,CTU1,F8A1,FUK, CPTP,LRFN3,MFSD10,C8orf82,MIB2,PGLS,PLA2G6, POLRMT,SPNS1,STK11,TAF6L,TIGD5,ZNF672,ZNF787

Co-Expressed gene's Protein-protein interaction Network Plot

: Open all plots for all cancer types

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Interacting Genes (from Pathway Commons)

: Open all interacting genes' information including KEGG pathway for all interacting genes from DAVID

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Pharmacological Information for STK11

Cross-referenced pharmacological DB IDs from Uniprot

DB Category	DB Name	DB's ID and Url link
Chemistry	BindingDB	Q15831; -.
Chemistry	ChEMBL	CHEMBL5606; -.
Chemistry	GuidetoPHARMACOLOGY	2212; -.
Organism-specific databases	PharmGKB	PA36198; -.
Organism-specific databases	CTD	6794; -.

Drug-Gene Interaction Network

* Gene Centered Interaction Network.

* Drug Centered Interaction Network.

DrugBank ID	Target Name	Drug Groups	Generic Name	Drug Centered Network	Drug Structure
DB00331	serine/threonine kinase 11	approved	Metformin

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Cross referenced IDs for STK11

* We obtained these cross-references from Uniprot database. It covers 150 different DBs, 18 categories. http://www.uniprot.org/help/cross_references_section

: Open all cross reference information