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 PIK3CA

Basic gene info.	Gene symbol	PIK3CA
	Gene name	phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha
	Synonyms	CLOVE\|CWS5\|MCAP\|MCM\|MCMTC\|PI3K\|p110-alpha
	Cytomap	UCSC genome browser: 3q26.3
	Genomic location	chr3 :178866310-178952497
	Type of gene	protein-coding
	RefGenes	NM_006218.2,
	Ensembl id	ENSG00000121879
	Description	PI3-kinase p110 subunit alphaPI3K-alphaphosphatidylinositol 3-kinase, catalytic, 110-KD, alphaphosphatidylinositol 3-kinase, catalytic, alpha polypeptidephosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoformphosphatidylinosito
	Modification date	20141222
dbXrefs	MIM : 171834
	HGNC : HGNC
	HPRD : 01382
Protein	UniProt: P42336 go to UniProt's Cross Reference DB Table
Expression	CleanEX: HS_PIK3CA
	BioGPS: 5290
	Gene Expression Atlas: ENSG00000121879
	The Human Protein Atlas: ENSG00000121879
Pathway	NCI Pathway Interaction Database: PIK3CA
	KEGG: PIK3CA
	REACTOME: PIK3CA
	ConsensusPathDB
	Pathway Commons: PIK3CA
Metabolism	MetaCyc: PIK3CA
	HUMANCyc: PIK3CA
Regulation	Ensembl's Regulation: ENSG00000121879
	miRBase: chr3 :178,866,310-178,952,497
	TargetScan: NM_006218
	cisRED: ENSG00000121879
Context	iHOP: PIK3CA
	cancer metabolism search in PubMed: PIK3CA
	UCL Cancer Institute: PIK3CA
Assigned class in ccmGDB	A - This gene has a literature evidence and it belongs to cancer gene.
References showing role of PIK3CA in cancer cell metabolism	1. Deming DA, Leystra AA, Farhoud M, Nettekoven L, Clipson L, et al. (2013) mTOR inhibition elicits a dramatic response in PI3K-dependent colon cancers. PLoS one 8: e60709. go to article 2. Fu X, Osborne CK, Schiff R (2013) Biology and therapeutic potential of PI3K signaling in ER+/HER2-negative breast cancer. The Breast 22: S12-S18. go to article

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Phenotypic Information for PIK3CA(metabolism pathway, cancer, disease, phenome)

Cancer Description
Cancer	CGAP: PIK3CA
	Familial Cancer Database: PIK3CA

* 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 BLCA ⁶, BRCA ⁷, COAD ⁸, CRC ⁹, ESO ¹⁰, GBM ¹¹, HNSC ¹², KIRC ¹³, LUAD ¹⁴, LUSC ¹⁵, UCEC ¹⁶, STAD ¹⁷, GBM ¹⁸, HNSC ¹⁹,	Therapeutic Vulnerabilities in Cancer²⁰

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.nature.com/nature/journal/vaop/ncurrent/full/nature12965.html,
7 http://www.nature.com/nature/journal/v490/n7418/full/nature11412.html,
8 http://www.nature.com/nature/journal/v487/n7407/full/nature11252.html,
9 http://www.nature.com/nature/journal/v505/n7484/full/nature12912.html,
10 http://www.nature.com/nature/journal/v505/n7484/full/nature12912.html,
11 http://www.sciencedirect.com/science/article/pii/S0092867413012087,
12 https://www.sciencemag.org/content/333/6046/1157,
13 http://www.nature.com/nature/journal/v499/n7456/full/nature12222.html,
14 http://www.sciencedirect.com/science/article/pii/S0092867412010227,
15 http://www.nature.com/nature/journal/v489/n7417/full/nature11404.html,
16 http://www.nature.com/nature/journal/v497/n7447/full/nature12113.html,
17 http://www.nature.com/nature/journal/v513/n7517/full/nature13480.html,
18 http://www.nejm.org/doi/full/10.1056/NEJMoa1402121,
19 http://www.nature.com/nature/journal/v517/n7536/full/nature14129.html,
20Therapeutic Vulnerabilities in Cancer; http://cbio.mskcc.org/cancergenomics/statius/

Metabolic Pathway Description
KEGG_INOSITOL_PHOSPHATE_METABOLISM KEGG_FC_GAMMA_R_MEDIATED_PHAGOCYTOSIS REACTOME_PHOSPHOLIPID_METABOLISM REACTOME_PI_METABOLISM REACTOME_METABOLISM_OF_LIPIDS_AND_LIPOPROTEINS

Others
OMIM	114480; phenotype. 114500; phenotype. 114550; phenotype. 167000; phenotype. 171834; gene. 182000; phenotype. 602501; phenotype. 612918; phenotype. 615108; phenotype.
Orphanet	140944; CLOVE syndrome. 144; Hereditary nonpolyposis colon cancer. 201; Cowden syndrome. 276280; Hemihyperplasia-multiple lipomatosis syndrome. 295239; Macrodactyly of fingers, unilateral. 295243; Macrodactyly of toes, unilateral. 314662; Segmental progressive overgrowth syndrome with fibroadipose hyperplasia. 60040; Megalencephaly-capillary malformation-polymicrogyria syndrome. 99802; Hemimegalencephaly.
Disease	KEGG Disease: PIK3CA
	MedGen: PIK3CA (Human Medical Genetics with Condition)
	ClinVar: PIK3CA
Phenotype	MGI: PIK3CA (International Mouse Phenotyping Consortium)
Phenotype	PhenomicDB: PIK3CA

Mutations for PIK3CA

* 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
pancreas	PIK3CA	chr3	178952260	178952280		chr3	177916014	177916034

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 PIK3CA 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
CV347577	DDX5	15	360	17	62498313	62499340	PIK3CA	351	627	3	178947888	178951983
BI870214	PPP2CA	108	328	5	133532781	133533001	PIK3CA	319	341	3	178893499	178893521

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	ns	ovary	pancre	prost	skin	stoma	thyro	urina
Total # sample	2			2	1		4		3		5						1
GAIN (# sample)	2			1			3		3		5						1
LOSS (# sample)				1	1		1

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=2893

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Somatic Mutation Counts per Tissue in COSMIC data

Stat. for Non-Synonymous SNVs (# total SNVs=6717)	Stat. for Synonymous SNVs (# total SNVs=182)

Stat. for Deletions (# total SNVs=32)	Stat. for Insertions (# total SNVs=30)

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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
chr3:178952085-178952085	p.H1047R	1918
chr3:178936091-178936091	p.E545Q	1181
chr3:178936082-178936082	p.E542K	766
chr3:178936092-178936092	p.E545A	224
chr3:178936094-178936094	p.Q546E	134
chr3:178916876-178916876	p.R88Q	89
chr3:178952074-178952074	p.M1043I	73
chr3:178936095-178936095	p.Q546R	70
chr3:178921553-178921553	p.N345K	67
chr3:178952084-178952084	p.H1047Y	54

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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=174

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	11	249	9	216	28		63		16	2		19	29	5		2	9	49	2	125
# mutation	11	43	4	209	23		23		11	2		17	18	5		2	8	34	2	73
nonsynonymous SNV	10	39	4	144	23		23		11	2		14	17	2		2	7	30	2	70
synonymous SNV	1	4		69								3	1	3			1	4		3

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
chr3:178952085	p.H1047R	169
chr3:178936091	p.E545K	129
chr3:178936082	p.E542K	74
chr3:178916876	p.R88Q	23
chr3:178921553	p.N345K	23
chr3:178936095	p.Q546R	20
chr3:178938934	p.E726K	18
chr3:178917478	p.G118D	16
chr3:178928079	p.E453Q	14
chr3:178927980	p.C420R	12

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 PIK3CA 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 PIK3CA

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


AGPAT4,AMTN,ARG2,NPAP1,ABRACL,CENPW,CSN3, DPPA5,FAM3D,FMO3,HEBP2,HIST1H4F,HYMAI,KCNMB2, KCNMB3,LOC285205,OR5AU1,PIK3CA,PWRN1,TRPC2,ZMAT3	ARHGAP42,CDC42BPA,EXOC6B,KATNAL1,KCTD20,KLHL20,LNPEP, MYCBP2,NR3C1,PBRM1,PIK3CA,PIKFYVE,PLEKHM3,PVRL3, RAPGEF2,RBMS3,REV3L,SAMD8,SBF2,SLC30A4,SOS1

AKAP2,BBX,CREBRF,FAM168A,FAM63B,HEG1,HIPK3, IL6ST,KIRREL,LRCH3,MYO5A,MYO9A,PIK3CA,PLEKHM3, RASA2,REST,SNX29,TAOK1,TCF4,TTBK2,UBXN7	AKAP11,ATF7,CLASP1,CRTC3,DSTYK,DYNC1LI2,ERC1, LAMC1,MACF1,MAP4,NAV2,NEK1,PDS5B,PIK3CA, PTPN11,ROCK1,ROR1,SACS,TEAD1,TTBK2,UBE2H

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 PIK3CA

Cross-referenced pharmacological DB IDs from Uniprot

DB Category	DB Name	DB's ID and Url link
Chemistry	BindingDB	P42336; -.
Chemistry	ChEMBL	CHEMBL2111367; -.
Chemistry	GuidetoPHARMACOLOGY	2153; -.
Organism-specific databases	PharmGKB	PA33308; -.
Organism-specific databases	CTD	5290; -.

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
DB08059	phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha	experimental	(1S,6BR,9AS,11R,11BR)-9A,11B-DIMETHYL-1-[(METHYLOXY)METHYL]-3,6,9-TRIOXO-1,6,6B,7,8,9,9A,10,11,11B-DECAHYDRO-3H-FURO[4,3,2-DE]INDENO[4,5-H][2]BENZOPYRAN-11-YL ACETATE
DB01248	phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha	approved; investigational	Docetaxel
DB00171	phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha	approved; nutraceutical	Adenosine triphosphate
DB00877	phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha	approved; investigational	Sirolimus
DB00122	phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha	approved; nutraceutical	Choline
DB00394	phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha	approved	Beclomethasone
DB00443	phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha	approved	Betamethasone
DB01222	phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha	approved; investigational	Budesonide
DB01410	phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha	approved; investigational	Ciclesonide
DB01260	phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha	approved; investigational	Desonide
DB01234	phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha	approved; investigational	Dexamethasone
DB00180	phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha	approved; investigational	Flunisolide
DB00588	phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha	approved; investigational	Fluticasone Propionate
DB00741	phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha	approved	Hydrocortisone
DB00959	phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha	approved	Methylprednisolone
DB00764	phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha	approved	Mometasone
DB01384	phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha	approved	Paramethasone
DB00860	phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha	approved	Prednisolone
DB00635	phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha	approved	Prednisone
DB00896	phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha	approved	Rimexolone
DB00620	phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha	approved	Triamcinolone
DB00131	phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha	approved; nutraceutical	Adenosine monophosphate
DB00125	phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha	approved; nutraceutical	L-Arginine
DB00155	phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha	approved; nutraceutical	L-Citrulline
DB00435	phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha	approved	Nitric Oxide
DB00864	phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha	approved; investigational	Tacrolimus
DB00619	phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha	approved	Imatinib

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Cross referenced IDs for PIK3CA

* 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