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 PDE8A

Basic gene info.	Gene symbol	PDE8A
	Gene name	phosphodiesterase 8A
	Synonyms	HsT19550
	Cytomap	UCSC genome browser: 15q25.3
	Genomic location	chr15 :85525204-85682372
	Type of gene	protein-coding
	RefGenes	NM_001243137.1, NM_002605.2,NM_173454.1,NM_173455.1,NM_173456.1, NM_173457.1,
	Ensembl id	ENSG00000073417
	Description	cAMP-specific cyclic nucleotide phosphodiesterase 8Ahigh affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A
	Modification date	20141207
dbXrefs	MIM : 602972
	HGNC : HGNC
	Ensembl : ENSG00000073417
	HPRD : 09114
	Vega : OTTHUMG00000148670
Protein	UniProt: go to UniProt's Cross Reference DB Table
Expression	CleanEX: HS_PDE8A
	BioGPS: 5151
	Gene Expression Atlas: ENSG00000073417
	The Human Protein Atlas: ENSG00000073417
Pathway	NCI Pathway Interaction Database: PDE8A
	KEGG: PDE8A
	REACTOME: PDE8A
	ConsensusPathDB
	Pathway Commons: PDE8A
Metabolism	MetaCyc: PDE8A
	HUMANCyc: PDE8A
Regulation	Ensembl's Regulation: ENSG00000073417
	miRBase: chr15 :85,525,204-85,682,372
	TargetScan: NM_001243137
	cisRED: ENSG00000073417
Context	iHOP: PDE8A
	cancer metabolism search in PubMed: PDE8A
	UCL Cancer Institute: PDE8A
Assigned class in ccmGDB	C

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Phenotypic Information for PDE8A(metabolism pathway, cancer, disease, phenome)

Cancer Description
Cancer	CGAP: PDE8A
	Familial Cancer Database: PDE8A

* 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	Therapeutic Vulnerabilities in Cancer¹

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,
1Therapeutic Vulnerabilities in Cancer; http://cbio.mskcc.org/cancergenomics/statius/

Metabolic Pathway Description
KEGG_PURINE_METABOLISM

Others
OMIM
Orphanet
Disease	KEGG Disease: PDE8A
	MedGen: PDE8A (Human Medical Genetics with Condition)
	ClinVar: PDE8A
Phenotype	MGI: PDE8A (International Mouse Phenotyping Consortium)
Phenotype	PhenomicDB: PDE8A

Mutations for PDE8A

* 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
breast	PDE8A	chr15	85528232	85528232		chr15	102064754	102064754
pancreas	PDE8A	chr15	85636627	85636647	PDE8A	chr15	85619168	85619188
pancreas	PDE8A	chr15	85638340	85638360		chr15	32068312	32068332
pancreas	PDE8A	chr15	85639984	85640004		chr15	97177916	97177936

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 PDE8A 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
BF770537	PDE8A	10	267	15	85645170	85645428	IPO5	257	386	13	98662387	98662516
BF951597	PDE8A	1	73	15	85666328	85666402	PDE8A	62	441	15	85660947	85666329
W92044	FAM20A	1	89	17	66531258	66531346	PDE8A	78	533	15	85681730	85682185
W91923	FAM20A	1	89	17	66531258	66531346	PDE8A	78	536	15	85681733	85682185

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=3

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Somatic Mutation Counts per Tissue in COSMIC data

Stat. for Non-Synonymous SNVs (# total SNVs=39)	Stat. for Synonymous SNVs (# total SNVs=13)

Stat. for Deletions (# total SNVs=0)	Stat. for Insertions (# total SNVs=0)
There's no deleted snv.	There's no inserted snv.

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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
chr15:85664054-85664054	p.V587V	2
chr15:85610364-85610364	p.L121L	2
chr15:85669540-85669540	p.P730S	2
chr15:85659274-85659274	p.R487W	1
chr15:85669546-85669546	p.R732*	1
chr15:85610343-85610343	p.Q114H	1
chr15:85661061-85661061	p.E575E	1
chr15:85619979-85619979	p.E169D	1
chr15:85666344-85666344	p.E669*	1
chr15:85656623-85656623	p.R377L	1

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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=2

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	1		9	1		1		4			3	6	2		1	5	8		7
# mutation	1	1		9	1		1		4			3	6	2		1	5	8		7
nonsynonymous SNV	1	1		3	1				4			3	5	1		1	3	6		5
synonymous SNV				6			1						1	1			2	2		2

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
chr15:85610364	p.L49L,PDE8A	2
chr15:85664158	p.D391N,PDE8A	1
chr15:85610390	p.G614G,PDE8A	1
chr15:85669590	p.G88C,PDE8A	1
chr15:85634368	p.L398F,PDE8A	1
chr15:85659299	p.D617G,PDE8A	1
chr15:85664166	p.R92M,PDE8A	1
chr15:85619125	p.R409R,PDE8A	1
chr15:85669605	p.T622I,PDE8A	1
chr15:85643406	p.R95T,PDE8A	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 PDE8A 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 PDE8A

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.

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


ADPGK,ARIH1,ASB7,BTBD1,DMXL2,FOXN2,GOLGA6L10, HMG20A,IDH3A,IREB2,MAN2A2,MAP2K1,MEF2A,MYO5A, PDE8A,PTPN9,RCN2,SLC41A2,VPS54,WHAMM,ZNF592	ACER3,ANO6,PQLC2L,CAT,CD36,CELF2,COL4A3BP, DDHD2,EBF1,EIF4EBP2,FERMT2,GNAI1,GTDC1,HRASLS5, MDFIC,PDE8A,PLIN1,RRAGC,SEPT11,SH3KBP1,UVRAG

ABCA5,ARFGEF2,EPB41L4B,TMEM236,KIAA1161,LRRK1,MAGI3, MCTP2,NR5A2,PDE8A,PHLPP2,PPARA,SEMA6D,SGK2, TRPM7,TUG1,USP53,ZNF587,ZNF592,ZNF774,ZNF91	AGFG2,AHCYL2,RHOV___CHP1,CPT1A,DTX4,EPB41L4B,FZD5, KIAA1522,LRRFIP2,MTMR11,MYO1D,NCEH1,PDE8A,PPM1B, RAPGEFL1,RAVER2,SGK2,SH3BGRL2,SLC26A2,SNX30,TMEM63B

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 PDE8A

Cross-referenced pharmacological DB IDs from Uniprot

DB Category

DB Name

DB's ID and Url link

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
DB00920	phosphodiesterase 8A	approved	Ketotifen
DB07954	phosphodiesterase 8A	experimental	3-ISOBUTYL-1-METHYLXANTHINE
DB01151	phosphodiesterase 8A	approved	Desipramine
DB00472	phosphodiesterase 8A	approved	Fluoxetine

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Cross referenced IDs for PDE8A

* 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