Massive interstitial copy-neutral loss-of-heterozygosity as evidence for cancer being a disease of the DNA-damage response

Kumar, Yogesh; Yang, Jianfeng; Hu, Taobo; Chen, Lei; Xu, Zhi; Xu, Lin; Hu, Xiao-Xia; Tang, Gusheng; Wang, Jian-Min; Li, Yi; Poon, Wai-Sang; Wan, Weiqing; Zhang, Liwei; Mat, Wai-Kin; Pun, Frank W.; Lee, Peggy; Cheong, Timothy H. Y.; Ding, Xiaofan; Ng, Siu-Kin; Tsang, Shui-Ying; Chen, Jin-Fei; Zhang, Peng; Li, Shao; Wang, Hong-Yang; Xue, Hong

doi:10.1186/s12920-015-0104-2

Table 2 Genes with LOH or GOH mutations in multiple cancer samples^a

From: Massive interstitial copy-neutral loss-of-heterozygosity as evidence for cancer being a disease of the DNA-damage response

A. Genes in TSGene database with LOH occurrence in three or more cancer samples^b
Chr ^c	Gene	Description	Samples with LOH sites ^e
6	AKAP12 ^d	A kinase (PRKA) anchor protein 12	Gastric1, Gastric3, Liver1
6	PARK2	Parkin RBR E3 ubiquitin protein ligase	Glioma3, Glioma5, Lung5
7	FBXL13	F-box and leucine-rich repeat protein 13	Glioma3, Liver1, Lung5
7	CUX1 ^d	Cut-like homeobox 1	Glioma5, Liver4, Lung5, Lung-Brain3
8	CSMD1 ^d	CUB and Sushi multiple domains 1	Gastric1, Glioma2 (2), Glioma3 (2), Liver1, Liver3, Liver5, Lung1, Lung5, Lung-Brain2 (1 + 1)
8	MFHAS1	Malignant fibrous histiocytoma amplified sequence 1	Gastric1, Liver4, Liver5
9	PPP2R4	Protein phosphatase 2A activator, regulatory subunit 4	Glioma1, Lung3, Lung5
9	PTPRD ^d	Protein tyrosine phosphatase, receptor type, D	Glioma1, Glioma3, Leukemia5, Liver1, Lung5 (3), Lung-Brain2
9	ROR2	Receptor tyrosine kinase-like orphan receptor 2	Gastric1 (3), Glioma3, Lung2
11	NUP98 ^d	Nucleoporin 98 kDa	Gastric3, Glioma3, Liver2, Lung-Brain1 (3)
12	CHFR	Checkpoint with forkhead and ring finger domains, E3 ubiquitin protein ligase	Glioma3, Liver2, Lung-Brain4
14	EGLN3	Egl-9 family hypoxia-inducible factor 3	Lung5 (1 + 1), Lung-Brain4, Lung-Brain5
16	DNAJA3	DnaJ (Hsp40) homolog, subfamily A, member 3	Liver4, Lung1, Lung5
16	AXIN1 ^d	Axin 1	Glioma2, Liver1, Lung5
19	GLTSCR1 ^d	Glioma tumor suppressor candidate region gene 1	Glioma5, Lung5, Lung-Brain4
22	PRR5	Proline rich 5 (renal)	Glioma3, Liver3, Lung5
B. Additional genes present in NCG4.0 database with LOH occurrence in three or more cancer samples ^b
Chr ^c	Gene	Description	Samples with LOH sites ^e
1	SMG5	SMG5 Nonsense Mediated MRNA Decay Factor	Liver2, Lung1, Lung5 (3), Lung-Brain2, Lung-Brain4
1	KAZN	Kazrin, Periplakin Interacting Protein	Gastric3, Liver1, Lung5, Lung-Brain2
2	CTNNA2	Catenin (Cadherin-Associated Protein), Alpha 2	Lung1, Lung3, Lung5 (2 + 2)
2	DPP10	Dipeptidyl-Peptidase 10 (Non-Functional)	Gastric1, Glioma3, Glioma5
3	ERC2	ELKS/RAB6-Interacting/CAST Family Member 2	Gastric3, Glioma3, Lung2
4	ELOVL6	ELOVL Fatty Acid Elongase 6	Glioma3, Glioma4, Lung-Brain2
4	FSTL5	Follistatin-Like 5	Glioma2, Lung5, Lung-Brain2
5	AFF4	AF4/FMR2 Family, Member 4	Gastric1, Glioma3, Lung5 (2)
5	DMGDH	Dimethylglycine Dehydrogenase	Gastric1, Liver5 (2), Lung2, Lung-Brain4
7	HIP1	Huntingtin Interacting Protein 1	Gastric1, Glioma5, Liver1, Liver4, Lung2, Lung5, Lung-Brain2
7	CARD11	Caspase Recruitment Domain Family, Member 11	Glioma2, Glioma5, Lung-Brain5
8	RIMS2	regulating synaptic membrane exocytosis 2	Glioma3 (1 + 1), Lung5, Liver5
9	FNBP1	Formin Binding Protein 1	Gastric5, Glioma5, Liver2 (2)
10	SORCS1	Sortilin-Related VPS10 Domain Containing Receptor 1	Gastric1, Glioma3, Liver4
10	CTNNA3	Catenin (Cadherin-Associated Protein), Alpha 3	Gastric1 (2), Glioma2, Lung-Brain1, Lung-Brain2
10	PFKP	Phosphofructokinase, Platelet	Glioma3, Lung5, Lung-Brain4
10	TACC2	Transforming, acidic coiled-coil containing protein 2	Gastric1, Lung2, Leukemia3, Liver4
10	DLG5	Discs, Large Homolog 5 (Drosophila)	Glioma5, Liver1, Lung5 (2)
10	TET1	Tet Methylcytosine Dioxygenase 1	Glioma3, Lung5 (4), Lung-Brain2 (1 + 1)
11	NUMA1	Nuclear Mitotic Apparatus Protein 1	Glioma2, Glioma4, Lung2
11	PGAP2	Post-GPI attachment to proteins 2	Lung4, Lung5, Liver2
13	FREM2	FRAS1 Related Extracellular Matrix Protein 2	Liver1, Lung2, Lung-Brain2
13	ZMYM2	Zinc Finger, MYM-Type 2	Gastric1, Liver1, Lung2
16	SLC38A8	Solute Carrier Family 38, Member 8	Glioma3, Glioma5, Lung-Brain2
16	RBFOX1	RNA Binding Protein, Fox-1 Homolog (C. Elegans) 1	Glioma3, Liver4, Lung5 (6)
17	SEPT9	Septin 9	Glioma1, Liver1, Lung5 (2)
17	CDK12	Cyclin-Dependent Kinase 12	Glioma5, Liver3, Lung5 (1 + 2)
17	DNAH9	Dynein, axonemal, heavy chain 9	Glioma3, Lung5 (2), Lung-Brain1, Lung-Brain4
17	GAS7	Growth Arrest-Specific 7	Gastric3 (2), Glioma2, Glioma3, Glioma4, Liver2, Lung-Brain4
17	RPS6KB1	Ribosomal Protein S6 Kinase, 70 kDa, Polypeptide 1	Gastric1, Liver2 (3), Liver4, Lung5
17	WIPF2	WAS/WASL Interacting Protein Family, Member 2	Liver2, Lung4, Lung-Brain2
18	MBP	Myelin Basic Protein	Gastric1, Glioma4, Lung5
18	LAMA1	Laminin, Alpha 1	Glioma3, Liver4, Lung5
18	LDLRAD4	Low Density Lipoprotein Receptor Class A Domain Containing 4	Gastric4, Glioma2, Glioma5, Lung5 (2), Lung-Brain4
18	GREB1L	Growth Regulation By Estrogen In Breast Cancer-Like	Liver4, Lung5, Lung-Brain2
19	GLTSCR1	Glioma Tumor Suppressor Candidate Region Gene 1	Glioma5, Lung-Brain4, Lung5
20	ZSWIM3	Zinc Finger, SWIM-Type Containing 3	Gastric1, Glioma3, Glioma5, Liver1
22	TRIOBP	TRIO And F-Actin Binding Protein	Glioma5, Lung5 (3), Lung-Brain2
C. Genes present in TSGene database with GOH occurrence in three or more cancer samples ^b
Chr ^c	Gene	Description	Samples with GOH sites
8	CSMD1 ^f	CUB and Sushi multiple domains 1	Gastric3 (2), Gastric4, Glioma3 (2), Lung5 (2)
9	PTPRD ^f	Protein Tyrosine Phosphatase, Receptor Type, D	Glioma1, Liver1, Lung5, Lung-Brain5
9	DAPK1	Death-Associated Protein Kinase 1	Glioma4, Liver1, Lung1
9	ROR2	Receptor Tyrosine Kinase-Like Orphan Receptor	Gastric5, Glioma5, Lung5 (2)
11	ST5	Suppression of Tumorigenicity 5	Glioma3, Glioma4, Glioma5
12	CHFR	Checkpoint with forkhead and ring finger domains, E3 ubiquitin protein ligase	Gastric1, Glioma5, Lung5 (3), Lung-Brain3
16	CDH1 ^f	Cadherin 1, Type 1, E-Cadherin (Epithelial)	Gastric2 (3), Lung5 (3), Lung-Brain4
22	CHEK2 ^f	Checkpoint kinase 2	Glioma3, Lung2, Lung5
D. Additional genes present in NCG4.0 database with GOH occurrence in three or more cancer samples ^b
Chr ^c	Gene	Description	Samples with GOH sites
1	KAZN	Kazrin, Periplakin Interacting Protein	Gastric4, Glioma4, Lung5 (4)
1	FMN2	Formin 2	Lung5, Liver1, Lung-Brain1
1	NLRP3	NLR Family, Pyrin Domain Containing 3	Glioma3 (3), Liver1 (2), Lung5
4	FSTL5	Follistatin-Like 5	Liver4, Lung2, Lung5 (2)
5	PCDHGC5	Protocadherin Gamma Subfamily C, 5	Liver2, Lung2, Lung5 (2)
7	KMT2C	Lysine (K)-Specific Methyltransferase 2C	Gastric2, Gastric5 (2), Leukemia4, Liver2, Liver4
9	FNBP1	Formin Binding Protein 1	Glioma5, Lung5, Lung-Brain1
9	TRPM6	Transient Receptor Potential Cation Channel, Subfamily M, Member 6	Glioma3, Liver4, Lung5
10	CTNNA3	Catenin (Cadherin-Associated Protein), Alpha 3	Glioma3, Liver1, Lung2, Lung5
10	PFKP	Phosphofructokinase, Platelet	Gastric1, Glioma1, Lung5
12	SP1	Sp1 Transcription Factor	Glioma3, Glioma4, Lung4 (2)
12	KDM2B	Lysine (K)-specific demethylase 2B	Glioma5, Lung5, Lung-Brain4
12	ERC1	ELKS/RAB6-Interacting/CAST Family Member 1	Gastric1, Lung2, Lung5, Liver5
13	ATP11A	ATPase, class VI, type 11A	Glioma3, Liver1, Liver2
16	CNOT1	CCR4-NOT Transcription Complex, Subunit 1	Glioma2, Glioma3, Lung5
16	SNX29	Sorting nexin 29	Gastric5, Lung5 (3), Liver1, Lung-Brain2
16	RBFOX1	RNA Binding Protein, Fox-1 Homolog (C. Elegans) 1	Gastric2, Glioma3 (4), Liver1 (2), Liver2, Lung4, Lung5 (3)
17	SEPT9	Septin 9	Liver1, Lung3, Lung5
17	RPS6KB1	Ribosomal Protein S6 Kinase, 70 kDa, Polypeptide 1	Gastric3, Glioma4, Lung-Brain3
17	TRIM37	Tripartite Motif Containing 37	Glioma1 (2), Glioma3, Glioma4
17	ITGAE	Integrin, Alpha E (Antigen CD103, Human Mucosal Lymphocyte Antigen 1; Alpha Polypeptide)	Glioma3, Glioma4 (2), Glioma5, Lung5 (2)
18	GREB1L	Growth Regulation By Estrogen In Breast Cancer-Like	Lung2, Lung4, Lung-Brain2 (2)
19	PTPRS	Protein tyrosine phosphatase, receptor type, S	Gastric1, Glioma5, Lung4
22	TUBA8	Tubulin, alpha 8	Gastric5, Glioma3, Lung5
E. Additional genes present in Ensemble database with extensive LOH occurrences ^g
	Gene	Description	Samples with LOH sites ^e
2	MTA3	Metastasis associated 1 family, member 3 [Source:HGNC Symbol;Acc:23784]	Gastric1, Lung-Brain2, Lung3 (2), Liver2, Lung-Brain3
3	EIF2B5	Eukaryotic translation initiation factor 2B, subunit 5 epsilon, 82 kDa [Source:HGNC Symbol;Acc:3261]	Glioma3, Lung5 (8), Liver5, Leukemia1
4	SMIM14	Small integral membrane protein 14 [Source:HGNC Symbol;Acc:27,321]	Liver2, Lung-Brain5, Glioma3, Leukemia5, Lung1 (2)
6	ATXN1	Ataxin 1 [Source:HGNC Symbol;Acc:10548]	Glioma5, Lung4, Lung5, Liver1, Lung-Brain5
6	RP11-146I2.1	Not Applicable	Glioma3, Lung3, Lung5, Liver2, Lung-Brain4
7	COL26A1	Collagen, type XXVI, alpha 1 [Source:HGNC Symbol;Acc:18038]	Gastric1, Lung1, Lung2, Liver1, Lung-Brain1
7	TYW1B	tRNA-yW synthesizing protein 1 homolog B (S. cerevisiae) [Source:HGNC Symbol;Acc:33908]	Gastric1, Glioma3, Glioma5, Lung1, Lung5
8	LOXL2	Lysyl oxidase-like 2 [Source:HGNC Symbol;Acc:6666]	Liver2 (2), Glioma3, Glioma4, Liver1, Liver3
8	RP11-124B13.1	Not Applicable	Gastric1, Glioma1, Glioma3, Lung2, Liver2
9	DMRT1	Doublesex and mab-3 related transcription factor 1 [Source:HGNC Symbol;Acc:2934]	Glioma5, Gastric3, Lung5, Glioma1, Gastric1, Lung-Brain2
9	ODF2	Outer dense fiber of sperm tails 2 [Source:HGNC Symbol;Acc:8114]	Lung-Brain2, Lung5 (2), Glioma5, Lung4, Lung-Brain4, Liver4
10	CAMK1D	Calcium/calmodulin-dependent protein kinase ID [Source:HGNC Symbol;Acc:19341]	Lung5 (4), Liver5, Glioma5 (2), Leukemia4, Lung-Brain4, Liver1 (1 + 1), Glioma3
10	FRMD4A	FERM domain containing 4A [Source:HGNC Symbol;Acc:25491]	Lung5 (2 + 8), Glioma5, Glioma3, Gastric1, Liver5
11	TMEM135	Transmembrane protein 135 [Source:HGNC Symbol;Acc:26167]	Gastric1, Glioma3, Glioma4, Glioma5, Lung3
14	KLC1	Kinesin light chain 1 [Source:HGNC Symbol;Acc:6387]	Liver5, Lung-Brain2, Gastric1, Glioma3, Liver2, Lung5
16	ABCC1	ATP-binding cassette, sub-family C (CFTR/MRP), member 1 [Source:HGNC Symbol;Acc:51]	Lung5 (2 + 2), Lung1, Liver2, Lung-Brain2, Lung-Brain1
16	C16orf45	Chromosome 16 open reading frame 45 [Source:HGNC Symbol;Acc:19213]	Gastric1, Glioma3, Lung2, Lung5, Lung-Brain5
17	NMT1	N-myristoyltransferase 1 [Source:HGNC Symbol;Acc:7857]	Glioma5, Liver4, Lung5 (2), Gastric1 (2), Glioma3,
17	PITPNC1	Phosphatidylinositol transfer protein, cytoplasmic 1 [Source:HGNC Symbol;Acc:21045]	Gastric1, Gastric4, Glioma3, Glioma5, Lung2
17	RAP1GAP2	RAP1 GTPase activating protein 2 [Source:HGNC Symbol;Acc:29176]	Liver2 (2), Glioma5 (2), Lung-Brain2 (2 + 1), Gastric5, Gastric1, Lung4, Lung5
17	RBFOX3	RNA binding protein, fox-1 homolog (C. elegans) 3 [Source:HGNC Symbol;Acc:27097]	Glioma3, Glioma5, Liver3, Lung-Brain4 (1 + 3), Lung-Brain5
18	DLGAP1	Discs, large (Drosophila) homolog-associated protein 1 [Source:HGNC Symbol;Acc:2905]	Lung-Brain2, Lung5 (2 + 1), Gastric4, Gastric1, Lung-Brain2, Glioma3
19	INSR	Insulin receptor [Source:HGNC Symbol;Acc:6091]	Liver3, Liver4, Lung2, Lung5 (1 + 1), Gastric1 (2)
19	SIPA1L3	Signal-induced proliferation-associated 1 like 3 [Source:HGNC Symbol;Acc:23801]	Glioma3, Lung-Brain2, Liver2, Lung5, Glioma3, Lung5
19	TDRD12	Tudor domain containing 12 [Source:HGNC Symbol;Acc:25044]	Lung-Brain1, Glioma5, Lung1, Glioma5, Glioma2, Liver2
19	GNG7	Guanine nucleotide binding protein (G protein), gamma 7 [Source:HGNC Symbol;Acc:4410]	Lung5 (1 + 7), Lung-Brain4 (3)
22	SYN3	Synapsin III [Source:HGNC Symbol;Acc:11496]	Lung3, Lung5, Lung-Brain4, Glioma3 (1 + 2), Glioma5
F. Additional genes present in Ensemble database with extensive GOH occurrences ^g
Chr ^c	Gene	Description	Samples with GOH sites ^e
1	RPRD2	Regulation of nuclear pre-mRNA domain containing 2 [Source:HGNC Symbol;Acc:29039]	Gastric2, Glioma3, Glioma4, Glioma5 (2), Liver1, Lung4, Lung5
1	CLSTN1	Calsyntenin 1 [Source:HGNC Symbol;Acc:17447]	Gastric5, Lung2, Lung5, Lung-Brain2, Lung-Brain4
1	KIF26B	Kinesin family member 26B [Source:HGNC Symbol;Acc:25484]	Liver3, Glioma3, Glioma5 (2), Lung5 (3), Gastric1
1	GON4L	Gon-4-like (C. elegans) [Source:HGNC Symbol;Acc:25973]	Lung2 (2), Lung5 (2), Glioma4 (2), Lung-Brain1, Gastric4
1	NMNAT2	Calsyntenin 1 [Source:HGNC Symbol;Acc:17447]	Glioma5, Lung1, Lung5, Liver1, Lung-Brain1
2	FAM178B	Family with sequence similarity 178, member B [Source:HGNC Symbol;Acc:28036]	Gastric5, Glioma3, Liver3, Liver5, Lung3
2	MTA3	Metastasis associated 1 family, member 3 [Source:HGNC Symbol;Acc:23784]	Glioma1, Glioma2, Glioma4, Liver1, Lung-Brain3
3	EIF2B5	Eukaryotic translation initiation factor 2B, subunit 5 epsilon, 82 kDa [Source:HGNC Symbol;Acc:3261]	Gastric3, Glioma5 (3), Lung5, Lung-Brain2, Lung-Brain4
4	AFAP1	Actin filament associated protein 1 [Source:HGNC Symbol;Acc:24017]	Glioma3 (2), Liver1, Lung5 (6), Leukemia4, Liver4, Glioma5
5	PDZD2	PDZ domain containing 2 [Source:HGNC Symbol;Acc:18486]	Lung2, Lung5 (4), Glioma1, Gastric2, Glioma3 (2)
5	PCDHGA1	Protocadherin gamma subfamily A, 1 [Source:HGNC Symbol;Acc:8696]	Glioma3, Glioma5, Liver2, Lung2, Lung5 (2)
7	CALN1	Calneuron 1 [Source:HGNC Symbol;Acc:13248]	Glioma3, Glioma3, Lung2 (5), Lung4, Lung5 (2)
7	KMT2C	Protocadherin gamma subfamily A, 1 [Source:HGNC Symbol;Acc:8696]	Gastric2, Gastric5 (2), Liver2, Liver4, Leukemia4
7	TYW1	tRNA-yW synthesizing protein 1 homolog (S. cerevisiae) [Source:HGNC Symbol;Acc:25598]	Glioma3, Glioma5 (3), Liver1, Lung-Brain1 (5)
8	PSD3	Pleckstrin and Sec7 domain containing 3 [Source:HGNC Symbol;Acc:19093]	Lung3, Lung5 (9)
10	CAMK1D	Calcium/calmodulin-dependent protein kinase ID [Source:HGNC Symbol;Acc:19341]	Glioma3, Liver1, Lung3, Lung4 (5), Lung5 (5), Glioma4
11	SHANK2	SH3 and multiple ankyrin repeat domains 2 [Source:HGNC Symbol;Acc:14295]	Glioma3, Lung3, Lung5, Liver1, Liver5
12	MPHOSPH9	M-phase phosphoprotein 9 [Source:HGNC Symbol;Acc:7215]	Leukemia3, Lung-Brain5, Lung2, Lung4 (2), Lung5, Glioma4
17	STX8	Syntaxin 8 [Source:HGNC Symbol;Acc:11443]	Glioma3, Glioma4 (2), Lung2, Lung4 (2), Leukemia2
17	USP43	SH3 and multiple ankyrin repeat domains 2 [Source:HGNC Symbol;Acc:14295]	Liver1, Lung2, Lung5, Glioma5, Lung-Brain4
19	INSR	Insulin receptor [Source:HGNC Symbol;Acc:6091]	Liver4, Glioma3 (2), Glioma4 (2), Lung-Brain3, Lung5 (3)
19	CTC-490E21.12	Not Applicable	Gastric2, Gastric3, Glioma4, Glioma5, Lung1
19	CTC-525D6.1	Not Applicable	Gastric2 (4), Lung5 (8)
19	SAE1	SUMO1 activating enzyme subunit 1 [Source:HGNC Symbol;Acc:30660]	Glioma3, Lung2, Lung4, Lung5, Liver1
20	ATP9A	ATPase, class II, type 9A [Source:HGNC Symbol;Acc:13540]	Liver1 (3), Glioma4, Gastric3, Lung4, Lung5 (2)
22	LARGE	Like-glycosyltransferase [Source:HGNC Symbol;Acc:6511]	Liver1 (2), Lung1, Lung2, Leukemia5 (2), Glioma5 (3), Gastric5 (2)
22	SGSM1	Lysine (K)-specific methyltransferase 2C [Source:HGNC Symbol;Acc:13726]	Gastric2, Glioma3, Leukemia5, Lung-Brain2 (2), Lung-Brain3

^aSee Additional file 9: Table S7A-F for complete lists of genes with LOH or GOH occurrence
^bTSGene: Tumor Suppressor Gene Database, containing 860 genes; NCG4.0: Network of Cancer Genes, containing 2000 genes
^c Chromosome on which the indicated gene is located
^dLOH-containing genes present in both TSGene and NCG4.0 databases are only listed in Table 2A but not Table 2B
^eThe bold-fonted LOH occurrences represent Mm-to-mm conversions, and the non-bold-fonted LOH occurrences represent Mm-to-MM conversions. Where a sample contained more than one LOH, the number of LOHs is indicated inside parenthesis, either in bold font for LOHs yielding mm genotypes, or in non-bold font for LOHs yielding MM genotypes
^fGOH-containing genes present in both TSGene and NCG4.0 databases are only listed in Table 2C but not Table 2D
^gThe list includes LOH- or GOH-bearing genes in Ensemble database (GRCh37.p13), which contains 57,736 genes, that are not in TSGene or NCG4.0

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