Colon/Rectal Adenocarcinoma: Mutation Analysis (MutSig)

Maintained by Dan DiCara (Broad Institute)

Overview

Introduction

This report serves to describe the mutational landscape and properties of a given individual set, as well as rank genes and genesets according to mutational significance. MutSig v1.5 was used to generate the results found in this report.

Working with individual set: COADREAD.

Number of patients in set: 224

Input

The input for this pipeline is a set of individuals with the following files associated for each:

1. An annotated .maf file describing the mutations called for the respective individual, and their properties.

2. A .wig file that contains information about the coverage of the sample.

Summary

Significantly mutated genes (q ≤ 0.1): 471

Mutations seen in COSMIC: 791

Significantly mutated genes in COSMIC territory: 29

Genes with clustered mutations (&le 3 aa apart): 1529

Significantly mutated genesets: 234

Significantly mutated genesets: (excluding sig. mutated genes): 44

Results

Breakdown of Mutations by Type

Table 1. Get Full Table Table representing breakdown of mutations by type.

type	count
De_novo_Start_InFrame	22
De_novo_Start_OutOfFrame	160
Frame_Shift_Del	1324
Frame_Shift_Ins	918
In_Frame_Del	166
In_Frame_Ins	28
Indel	2
Missense_Mutation	54509
Nonsense_Mutation	5376
Nonstop_Mutation	12
Read-through	34
Silent	19249
Splice_Site	205
Start_Codon_DNP	2
Total	82007

Breakdown of Mutation Rates by Category Type

Table 2. Get Full Table A breakdown of mutation rates per category discovered for this individual set.

category	n	N	rate	rate_per_mb	relative_rate
*CpG->T	20515	369939104	0.000055	55	5.9
*Cp(A/C/T)->mut	21185	3041594232	7e-06	7	0.74
A->mut	12242	3284997724	3.7e-06	3.7	0.4
*CpG->(G/A)	568	369939104	1.5e-06	1.5	0.16
indel+null	7583	6696531284	1.1e-06	1.1	0.12
double_null	665	6696531284	9.9e-08	0.099	0.011
Total	62758	6696531284	9.4e-06	9.4	1

Target Coverage for Each Individual

The x axis represents the samples. The y axis represents the exons, one row per exon, and they are sorted by average coverage across samples. For exons with exactly the same average coverage, they are sorted next by the %GC of the exon. (The secondary sort is especially useful for the zero-coverage exons at the bottom).

Figure 1.

Distribution of Mutation Counts, Coverage, and Mutation Rates Across Samples

Figure 2.

Significantly Mutated Genes

Table 3. Get Full Table A Ranked List of Significantly Mutated Genes. Number of significant genes found: 471. Number of genes displayed: 35

rank	gene	description	N	n	npat	nsite	nsil	n1	n2	n3	n4	n5	n6	p	q
1	APC	adenomatous polyposis coli	1924608	241	160	151	4	6	15	11	0	103	106	<1.00e-15	<6.01e-12
2	TP53	tumor protein p53	289720	122	120	69	2	48	22	12	2	38	0	<1.00e-15	<6.01e-12
3	KRAS	v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog	158368	96	96	11	0	0	91	4	0	1	0	<1.00e-15	<6.01e-12
4	FBXW7	F-box and WD repeat domain containing 7	578816	45	38	28	2	23	6	5	2	9	0	6.33e-15	2.85e-11
5	SMAD4	SMAD family member 4	381472	30	26	23	0	10	6	9	0	3	2	4.42e-14	1.04e-10
6	FAM123B	family with sequence similarity 123B	743964	27	25	24	2	1	3	4	0	19	0	4.61e-14	1.04e-10
7	NRAS	neuroblastoma RAS viral (v-ras) oncogene homolog	131264	20	20	8	0	2	14	4	0	0	0	4.61e-14	1.04e-10
8	SMAD2	SMAD family member 2	323456	16	15	12	1	3	5	3	0	5	0	5.60e-14	1.04e-10
9	PIK3CA	phosphoinositide-3-kinase, catalytic, alpha polypeptide	736288	40	33	21	2	6	20	14	0	0	0	5.68e-14	1.04e-10
10	LRP1B	low density lipoprotein-related protein 1B (deleted in tumors)	3172736	79	39	77	18	11	34	23	0	5	6	5.78e-14	1.04e-10
11	TCF7L2	transcription factor 7-like 2 (T-cell specific, HMG-box)	453708	20	18	18	4	5	5	3	0	7	0	7.23e-14	1.18e-10
12	BRAF	v-raf murine sarcoma viral oncogene homolog B1	499744	23	22	4	0	0	0	23	0	0	0	2.01e-13	3.02e-10
13	ARID1A	AT rich interactive domain 1A (SWI-like)	1311268	22	21	20	3	2	5	1	1	13	0	2.97e-11	4.12e-08
14	TTN	titin	24865216	309	86	304	78	82	114	72	3	13	25	4.97e-11	6.24e-08
15	PCDH9	protocadherin 9	835520	26	22	26	7	3	11	11	0	1	0	5.19e-11	6.24e-08
16	WBSCR17	Williams-Beuren syndrome chromosome region 17	403312	19	19	18	3	10	5	1	0	3	0	1.30e-10	1.47e-07
17	DMD	dystrophin (muscular dystrophy, Duchenne and Becker types)	2608328	47	33	46	6	10	14	14	0	9	0	1.60e-10	1.70e-07
18	ATM	ataxia telangiectasia mutated	2109720	39	25	37	3	4	18	5	0	6	6	2.46e-10	2.46e-07
19	ZC3H13	zinc finger CCCH-type containing 13	1066016	26	21	25	1	8	2	1	0	15	0	8.77e-10	8.02e-07
20	FAT4	FAT tumor suppressor homolog 4 (Drosophila)	3346084	74	40	74	21	19	30	19	1	5	0	8.89e-10	8.02e-07
21	LIFR	leukemia inhibitory factor receptor alpha	754200	24	18	24	5	4	6	9	1	4	0	3.69e-09	3.17e-06
22	ACVR1B	activin A receptor, type IB	340816	15	14	15	0	4	7	2	0	2	0	5.29e-09	4.33e-06
23	MAP2K4	mitogen-activated protein kinase kinase 4	252000	11	11	10	1	3	4	2	0	2	0	1.60e-08	0.000013
24	TXNDC3	thioredoxin domain containing 3 (spermatozoa)	409248	14	11	14	2	3	3	3	0	5	0	7.79e-08	0.000058
25	CNTN6	contactin 6	711200	22	17	22	3	5	13	2	0	2	0	1.01e-07	0.000073
26	KLHL4	kelch-like 4 (Drosophila)	508704	16	16	16	3	6	8	2	0	0	0	1.09e-07	0.000075
27	BAI3	brain-specific angiogenesis inhibitor 3	1046976	23	18	21	6	3	10	6	1	3	0	1.37e-07	0.000090
28	SYNE1	spectrin repeat containing, nuclear envelope 1	6063232	102	47	100	30	23	42	27	0	7	3	1.39e-07	0.000090
29	SOX9	SRY (sex determining region Y)-box 9 (campomelic dysplasia, autosomal sex-reversal)	268720	11	10	11	0	0	0	1	0	8	2	1.45e-07	0.000090
30	CPXCR1	CPX chromosome region, candidate 1	203840	10	9	10	1	2	5	2	0	1	0	1.96e-07	0.00012
31	PRDM9	PR domain containing 9	610400	20	16	20	4	6	7	4	0	1	2	2.03e-07	0.00012
32	KIAA1804		540708	18	15	16	0	8	7	1	0	2	0	2.17e-07	0.00012
33	ACVR2A	activin A receptor, type IIA	355264	11	9	10	1	0	0	4	0	5	2	2.84e-07	0.00016
34	SLITRK1	SLIT and NTRK-like family, member 1	469280	17	15	16	5	6	2	6	0	3	0	3.05e-07	0.00016
35	DNAH5	dynein, axonemal, heavy chain 5	3138008	70	34	68	15	25	25	11	1	4	4	4.41e-07	0.00023

Note:

N - number of sequenced bases in this gene across the individual set.

n - number of (nonsilent) mutations in this gene across the individual set.

npat - number of patients (individuals) with at least one nonsilent mutation.

nsite - number of unique sites having a non-silent mutation.

nsil - number of silent mutations in this gene across the individual set.

n1 - number of nonsilent mutations of type: *CpG->T .

n2 - number of nonsilent mutations of type: *Cp(A/C/T)->mut .

n3 - number of nonsilent mutations of type: A->mut .

n4 - number of nonsilent mutations of type: *CpG->(G/A) .

n5 - number of nonsilent mutations of type: indel+null .

null - mutation category that includes nonsense, frameshift, splice-site mutations

p_classic = p-value for the observed amount of nonsilent mutations being elevated in this gene

p_ns_s = p-value for the observed nonsilent/silent ratio being elevated in this gene

p = p-value (overall)

q = q-value, False Discovery Rate (Benjamini-Hochberg procedure)

COSMIC analyses

In this analysis, COSMIC is used as a filter to increase power by restricting the territory of each gene. Cosmic version: v48.

Table 4. Get Full Table Significantly mutated genes (COSMIC territory only). To access the database please go to: COSMIC. Number of significant genes found: 29. Number of genes displayed: 10

rank	gene	description	n	cos	n_cos	N_cos	cos_ev	p	q
1	APC	adenomatous polyposis coli	241	838	187	187712	5628	0	0
2	TP53	tumor protein p53	122	823	122	184352	45406	0	0
3	ERBB3	v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian)	14	6	6	1344	6	7.3e-15	1e-11
4	NRAS	neuroblastoma RAS viral (v-ras) oncogene homolog	20	28	18	6272	17998	9.2e-15	1e-11
5	KRAS	v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog	96	51	95	11424	1013913	1.6e-14	1.4e-11
6	BRAF	v-raf murine sarcoma viral oncogene homolog B1	23	88	20	19712	210160	2.5e-14	1.7e-11
7	FBXW7	F-box and WD repeat domain containing 7	45	91	31	20384	1228	2.6e-14	1.7e-11
8	SMAD4	SMAD family member 4	30	159	19	35616	90	4e-14	2.2e-11
9	PIK3CA	phosphoinositide-3-kinase, catalytic, alpha polypeptide	40	184	34	41216	13256	4.4e-14	2.2e-11
10	KRTAP5-5	keratin associated protein 5-5	4	1	4	224	4	7.9e-13	3.6e-10

Note:

n - number of (nonsilent) mutations in this gene across the individual set.

cos = number of unique mutated sites in this gene in COSMIC

n_cos = overlap between n and cos.

N_cos = number of individuals times cos.

cos_ev = total evidence: number of reports in COSMIC for mutations seen in this gene.

p = p-value for seeing the observed amount of overlap in this gene)

q = q-value, False Discovery Rate (Benjamini-Hochberg procedure)

Clustered Mutations

Table 5. Get Full Table Genes with Clustered Mutations

num	gene	desc	n	npairs3	npairs12
6684	KRAS	v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog	96	2964	3043
13084	TP53	tumor protein p53	122	389	720
648	APC	adenomatous polyposis coli	241	384	650
1263	BRAF	v-raf murine sarcoma viral oncogene homolog B1	23	190	190
9500	PIK3CA	phosphoinositide-3-kinase, catalytic, alpha polypeptide	40	89	134
4557	FBXW7	F-box and WD repeat domain containing 7	45	86	104
8433	NRAS	neuroblastoma RAS viral (v-ras) oncogene homolog	20	73	73
11794	SMAD4	SMAD family member 4	30	28	58
4126	ERBB3	v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian)	14	15	15
4382	FAM22F	family with sequence similarity 22, member F	10	15	15

Note:

n - number of mutations in this gene in the individual set.

mindist - distance (in aa) between closest pair of mutations in this gene

npairs3 - how many pairs of mutations are within 3 aa of each other.

npairs12 - how many pairs of mutations are within 12 aa of each other.

Geneset Analyses

Table 6. Get Full Table A Ranked List of Significantly Mutated Genesets. (Source: MSigDB GSEA Cannonical Pathway Set).Number of significant genesets found: 234. Number of genesets displayed: 10

rank	geneset	description	genes	N_genes	mut_tally	N	n	npat	nsite	nsil	n1	n2	n3	n4	n5	n6	p	q
1	HSA04310_WNT_SIGNALING_PATHWAY	Genes involved in Wnt signaling pathway	APC, APC2, AXIN1, AXIN2, BTRC, CACYBP, CAMK2A, CAMK2B, CAMK2D, CAMK2G, CCND1, CCND2, CCND3, CER1, CHD8, CHP, CREBBP, CSNK1A1, CSNK1A1L, CSNK1E, CSNK2A1, CSNK2A2, CSNK2B, CTBP1, CTBP2, CTNNB1, CTNNBIP1, CUL1, CXXC4, DAAM1, DAAM2, DKK1, DKK2, DKK4, DVL1, DVL2, DVL3, EP300, FBXW11, FOSL1, FRAT1, FRAT2, FZD1, FZD10, FZD2, FZD3, FZD4, FZD5, FZD6, FZD7, FZD8, FZD9, GSK3B, JUN, LEF1, LOC652788, LRP5, LRP6, MAP3K7, MAPK10, MAPK8, MAPK9, MMP7, MYC, NFAT5, NFATC1, NFATC2, NFATC3, NFATC4, NKD1, NKD2, NLK, PLCB1, PLCB2, PLCB3, PLCB4, PORCN, PPARD, PPP2CA, PPP2CB, PPP2R1A, PPP2R1B, PPP2R2A, PPP2R2B, PPP2R2C, PPP3CA, PPP3CB, PPP3CC, PPP3R1, PPP3R2, PRICKLE1, PRICKLE2, PRKACA, PRKACB, PRKACG, PRKCA, PRKCB1, PRKCG, PRKX, PRKY, PSEN1, RAC1, RAC2, RAC3, RBX1, RHOA, ROCK1, ROCK2, RUVBL1, SENP2, SFRP1, SFRP2, SFRP4, SFRP5, SIAH1, SKP1, SMAD2, SMAD3, SMAD4, SOX17, TBL1X, TBL1XR1, TBL1Y, TCF7, TCF7L1, TCF7L2, TP53, VANGL1, VANGL2, WIF1, WNT1, WNT10A, WNT10B, WNT11, WNT16, WNT2, WNT2B, WNT3, WNT3A, WNT4, WNT5A, WNT5B, WNT6, WNT7A, WNT7B, WNT8A, WNT8B, WNT9A, WNT9B	144	APC(241), APC2(1), AXIN1(2), AXIN2(9), BTRC(5), CACYBP(2), CAMK2A(1), CAMK2B(2), CAMK2D(3), CAMK2G(2), CCND2(1), CCND3(1), CER1(3), CHD8(6), CREBBP(25), CSNK1A1(2), CSNK1A1L(5), CSNK2A1(4), CSNK2A2(2), CSNK2B(2), CTBP1(1), CTBP2(2), CTNNB1(12), CTNNBIP1(1), CUL1(9), CXXC4(1), DAAM1(2), DAAM2(9), DKK1(5), DKK2(6), DKK4(7), DVL2(9), DVL3(4), EP300(15), FBXW11(8), FZD1(1), FZD10(6), FZD2(2), FZD3(13), FZD4(2), FZD6(6), FZD7(3), FZD8(1), GSK3B(8), LEF1(4), LRP5(5), LRP6(17), MAP3K7(4), MAPK10(8), MAPK8(7), MAPK9(5), MMP7(5), NFAT5(5), NFATC1(2), NFATC2(6), NFATC3(5), NFATC4(5), NKD1(3), NKD2(1), NLK(2), PLCB1(8), PLCB2(3), PLCB3(4), PLCB4(10), PORCN(2), PPARD(2), PPP2CA(1), PPP2CB(2), PPP2R1A(5), PPP2R1B(2), PPP2R2A(1), PPP2R2B(3), PPP2R2C(4), PPP3CA(3), PPP3CB(5), PPP3CC(4), PPP3R1(1), PPP3R2(1), PRICKLE1(11), PRICKLE2(6), PRKACA(1), PRKACB(1), PRKACG(3), PRKCA(4), PRKCG(10), PRKX(2), PSEN1(3), RBX1(1), RHOA(5), ROCK1(15), ROCK2(6), RUVBL1(8), SENP2(3), SFRP1(3), SFRP2(3), SFRP4(4), SFRP5(1), SIAH1(1), SKP1(1), SMAD2(16), SMAD3(9), SMAD4(30), SOX17(2), TBL1X(6), TBL1XR1(6), TBL1Y(1), TCF7(6), TCF7L1(3), TCF7L2(20), TP53(122), VANGL1(2), VANGL2(5), WIF1(2), WNT1(1), WNT10B(4), WNT11(3), WNT16(2), WNT2(1), WNT2B(3), WNT3(4), WNT3A(1), WNT4(1), WNT5A(3), WNT6(1), WNT7A(2), WNT7B(2), WNT8A(2), WNT9A(2), WNT9B(2)	54356112	953	218	786	158	276	207	133	8	221	108	<1.00e-15	<2.68e-14
2	HSA04810_REGULATION_OF_ACTIN_CYTOSKELETON	Genes involved in regulation of actin cytoskeleton	ABI2, ACTN1, ACTN2, ACTN3, ACTN4, APC, APC2, ARAF, ARHGEF1, ARHGEF12, ARHGEF4, ARHGEF6, ARHGEF7, ARPC1A, ARPC1B, ARPC2, ARPC3, ARPC4, ARPC5, ARPC5L, BAIAP2, BCAR1, BDKRB1, BDKRB2, BRAF, C3orf10, CD14, CDC42, CFL1, CFL2, CHRM1, CHRM2, CHRM3, CHRM4, CHRM5, CRK, CRKL, CSK, CYFIP1, CYFIP2, DIAPH1, DIAPH2, DIAPH3, DOCK1, EGF, EGFR, EZR, F2, F2R, FGD1, FGD3, FGF1, FGF10, FGF11, FGF12, FGF13, FGF14, FGF16, FGF17, FGF18, FGF19, FGF2, FGF20, FGF21, FGF22, FGF23, FGF3, FGF4, FGF5, FGF6, FGF7, FGF8, FGF9, FGFR1, FGFR2, FGFR3, FGFR4, FN1, GIT1, GNA12, GNA13, GNG12, GRLF1, GSN, HRAS, INS, IQGAP1, IQGAP2, IQGAP3, ITGA1, ITGA10, ITGA11, ITGA2, ITGA2B, ITGA3, ITGA4, ITGA5, ITGA6, ITGA7, ITGA8, ITGA9, ITGAD, ITGAE, ITGAL, ITGAM, ITGAV, ITGAX, ITGB1, ITGB2, ITGB3, ITGB4, ITGB5, ITGB6, ITGB7, ITGB8, KRAS, LIMK1, LIMK2, LOC200025, LOC645126, LOC653888, MAP2K1, MAP2K2, MAPK1, MAPK3, MLCK, MOS, MRAS, MRCL3, MRLC2, MSN, MYH10, MYH14, MYH9, MYL2, MYL5, MYL7, MYL8P, MYL9, MYLC2PL, MYLK, MYLK2, MYLPF, NCKAP1, NCKAP1L, NRAS, PAK1, PAK2, PAK3, PAK4, PAK6, PAK7, PDGFA, PDGFB, PDGFRA, PDGFRB, PFN1, PFN2, PFN3, PFN4, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, PIP4K2A, PIP4K2B, PIP4K2C, PIP5K1A, PIP5K1B, PIP5K1C, PIP5K3, PPP1CA, PPP1CB, PPP1CC, PPP1R12A, PPP1R12B, PTK2, PXN, RAC1, RAC2, RAC3, RAF1, RDX, RHOA, ROCK1, ROCK2, RRAS, RRAS2, SCIN, SLC9A1, SOS1, SOS2, SSH1, SSH2, SSH3, TIAM1, TIAM2, TMSB4X, TMSB4Y, TMSL3, VAV1, VAV2, VAV3, VCL, WAS, WASF1, WASF2, WASL	203	ABI2(1), ACTN1(5), ACTN2(8), ACTN3(3), ACTN4(3), APC(241), APC2(1), ARAF(3), ARHGEF1(5), ARHGEF12(9), ARHGEF4(4), ARHGEF6(10), ARHGEF7(8), ARPC1A(5), ARPC1B(2), ARPC2(2), ARPC5(1), ARPC5L(2), BAIAP2(2), BDKRB2(3), BRAF(23), CD14(1), CDC42(1), CFL1(1), CHRM1(3), CHRM2(11), CHRM3(4), CHRM4(1), CHRM5(2), CRKL(2), CSK(4), CYFIP1(6), CYFIP2(5), DIAPH1(1), DIAPH2(12), DIAPH3(5), DOCK1(7), EGF(3), EGFR(12), EZR(2), F2(4), F2R(1), FGD1(8), FGD3(2), FGF1(2), FGF11(3), FGF12(3), FGF13(3), FGF14(5), FGF17(1), FGF19(1), FGF20(2), FGF21(2), FGF23(1), FGF3(1), FGF5(4), FGF6(3), FGF7(1), FGF8(1), FGF9(1), FGFR1(4), FGFR2(6), FGFR3(2), FGFR4(2), FN1(22), GIT1(3), GNA12(2), GNA13(2), GRLF1(12), IQGAP1(13), IQGAP2(12), IQGAP3(12), ITGA1(3), ITGA10(7), ITGA11(4), ITGA2(6), ITGA2B(4), ITGA3(4), ITGA4(8), ITGA5(7), ITGA6(4), ITGA7(6), ITGA8(8), ITGA9(6), ITGAD(8), ITGAE(7), ITGAL(8), ITGAM(8), ITGAV(5), ITGAX(6), ITGB1(6), ITGB2(5), ITGB3(9), ITGB4(3), ITGB5(6), ITGB6(6), ITGB7(4), ITGB8(5), KRAS(96), LIMK1(5), LIMK2(5), MAP2K1(4), MAP2K2(1), MAPK1(2), MAPK3(3), MOS(3), MRAS(1), MSN(6), MYH10(10), MYH14(12), MYH9(12), MYL2(1), MYL7(1), MYL9(2), MYLK(14), MYLK2(3), NCKAP1(9), NCKAP1L(11), NRAS(20), PAK1(5), PAK2(3), PAK3(5), PAK6(1), PAK7(7), PDGFA(1), PDGFRA(18), PDGFRB(6), PFN2(1), PFN4(1), PIK3CA(40), PIK3CB(2), PIK3CD(3), PIK3CG(14), PIK3R1(12), PIK3R2(1), PIK3R3(4), PIK3R5(1), PIP4K2A(2), PIP4K2B(2), PIP4K2C(3), PIP5K1A(3), PIP5K1B(2), PIP5K1C(4), PPP1CB(2), PPP1CC(2), PPP1R12A(3), PPP1R12B(9), PTK2(6), RAF1(6), RDX(3), RHOA(5), ROCK1(15), ROCK2(6), RRAS2(2), SCIN(3), SLC9A1(4), SOS1(7), SOS2(11), SSH1(6), SSH2(4), SSH3(1), TIAM1(19), TIAM2(16), TMSL3(1), VAV1(13), VAV2(4), VAV3(12), VCL(2), WAS(1), WASF1(3), WASF2(2), WASL(7)	94731820	1255	217	1019	278	337	395	205	8	196	114	<1.00e-15	<2.68e-14
3	ST_ADRENERGIC	Adrenergic receptors respond to epinephrine and norepinephrine signaling.	AKT1, APC, AR, ASAH1, BF, BRAF, CAMP, CCL13, CCL15, CCL16, DAG1, EGFR, GAS, GNA11, GNA15, GNAI1, GNAQ, ITPKA, ITPKB, ITPR1, ITPR2, ITPR3, KCNJ3, KCNJ5, KCNJ9, MAPK1, MAPK10, MAPK14, PHKA2, PIK3CA, PIK3CD, PIK3R1, PITX2, PTX1, PTX3, RAF1, SRC	34	AKT1(2), APC(241), AR(6), ASAH1(3), BRAF(23), CCL13(1), CCL15(1), DAG1(5), EGFR(12), GNA11(1), GNA15(3), GNAI1(4), GNAQ(4), ITPKB(4), ITPR1(19), ITPR2(19), ITPR3(12), KCNJ3(6), KCNJ5(4), KCNJ9(3), MAPK1(2), MAPK10(8), MAPK14(3), PHKA2(7), PIK3CA(40), PIK3CD(3), PIK3R1(12), PITX2(2), PTX3(2), RAF1(6), SRC(3)	18222276	461	191	331	62	78	75	76	0	120	112	<1.00e-15	<2.68e-14
4	WNT_SIGNALING	Wnt signaling genes	APC, ARHA, AXIN1, C2orf31, CCND1, CCND2, CCND3, CSNK1E, CSNK1E, LOC400927, CTNNB1, DIPA, DVL1, DVL2, DVL3, FBXW2, FOSL1, FRAT1, FZD1, FZD10, FZD2, FZD3, FZD5, FZD6, FZD7, FZD8, FZD9, GSK3B, JUN, LDLR, MAPK10, MAPK9, MYC, PAFAH1B1, PLAU, PPP2R5C, PPP2R5E, PRKCA, PRKCB1, PRKCD, PRKCE, PRKCG, PRKCH, PRKCI, PRKCM, PRKCQ, PRKCZ, PRKD1, RAC1, RHOA, SFRP4, TCF7, WNT1, WNT10A, WNT10B, WNT11, WNT16, WNT2, WNT2B, WNT3, WNT4, WNT5A, WNT5B, WNT6, WNT7A, WNT7B	58	APC(241), AXIN1(2), CCND2(1), CCND3(1), CTNNB1(12), DVL2(9), DVL3(4), FBXW2(3), FZD1(1), FZD10(6), FZD2(2), FZD3(13), FZD6(6), FZD7(3), FZD8(1), GSK3B(8), LDLR(5), MAPK10(8), MAPK9(5), PAFAH1B1(3), PLAU(3), PPP2R5C(3), PPP2R5E(2), PRKCA(4), PRKCD(3), PRKCE(6), PRKCG(10), PRKCH(3), PRKCI(4), PRKCQ(5), PRKD1(15), RHOA(5), SFRP4(4), TCF7(6), WNT1(1), WNT10B(4), WNT11(3), WNT16(2), WNT2(1), WNT2B(3), WNT3(4), WNT4(1), WNT5A(3), WNT6(1), WNT7A(2), WNT7B(2)	19830148	434	187	340	62	83	73	42	2	128	106	<1.00e-15	<2.68e-14
5	ALKPATHWAY	Activin receptor-like kinase 3 (ALK3) is required during gestation for cardiac muscle development.	ACVR1, APC, ATF2, AXIN1, BMP10, BMP2, BMP4, BMP5, BMP7, BMPR1A, BMPR2, CHRD, CTNNB1, DVL1, FZD1, GATA4, GSK3B, MADH1, MADH4, MADH5, MADH6, MAP3K7, MEF2C, MYL2, NKX2-5, NOG, NPPA, NPPB, RFC1, TCF1, TGFB1, TGFB2, TGFB3, TGFBR1, TGFBR2, TGFBR3, WNT1	32	ACVR1(4), APC(241), ATF2(1), AXIN1(2), BMP10(3), BMP2(1), BMP4(2), BMP5(5), BMP7(6), BMPR1A(4), BMPR2(11), CHRD(5), CTNNB1(12), FZD1(1), GATA4(1), GSK3B(8), MAP3K7(4), MEF2C(9), MYL2(1), NKX2-5(1), NPPA(1), NPPB(1), RFC1(14), TGFB1(1), TGFB2(9), TGFBR1(9), TGFBR2(7), TGFBR3(8), WNT1(1)	12081204	373	185	280	34	50	54	35	1	127	106	<1.00e-15	<2.68e-14
6	ST_WNT_BETA_CATENIN_PATHWAY	Beta-catenin is degraded in the absence of Wnt signaling; when extracellular Wnt binds Frizzled receptors, beta-catenin accumulates in the nucleus and may promote cell survival.	AKT1, AKT2, AKT3, ANKRD6, APC, AXIN1, AXIN2, C22orf2, CER1, CSNK1A1, CTNNB1, DACT1, DKK1, DKK2, DKK3, DKK4, DVL1, FRAT1, FSTL1, GSK3A, GSK3B, IDAX, LAMR1, LRP1, MVP, NKD1, NKD2, PIN1, PSEN1, PTPRA, SENP2, SFRP1, TSHB, WIF1	30	AKT1(2), AKT2(6), AKT3(1), ANKRD6(5), APC(241), AXIN1(2), AXIN2(9), CER1(3), CSNK1A1(2), CTNNB1(12), DACT1(6), DKK1(5), DKK2(6), DKK3(2), DKK4(7), FSTL1(6), GSK3A(2), GSK3B(8), LRP1(18), MVP(4), NKD1(3), NKD2(1), PIN1(1), PSEN1(3), PTPRA(2), SENP2(3), SFRP1(3), TSHB(1), WIF1(2)	13605284	366	185	273	37	60	43	39	1	117	106	<1.00e-15	<2.68e-14
7	GSK3PATHWAY	Bacterial lipopolysaccharide activates AKT to promote the survival and activation of macrophages and inhibits Gsk3-beta to promote beta-catenin accumulation in the nucleus.	AKT1, APC, AXIN1, CCND1, CD14, CTNNB1, DVL1, FZD1, GJA1, GNAI1, GSK3B, IRAK1, LBP, LEF1, LY96, MYD88, NFKB1, PDPK1, PIK3CA, PIK3R1, PPP2CA, PRKR, RELA, TIRAP, TLR4, TOLLIP, WNT1	26	AKT1(2), APC(241), AXIN1(2), CD14(1), CTNNB1(12), FZD1(1), GJA1(8), GNAI1(4), GSK3B(8), IRAK1(1), LBP(1), LEF1(4), LY96(2), MYD88(2), NFKB1(6), PDPK1(1), PIK3CA(40), PIK3R1(12), PPP2CA(1), RELA(2), TIRAP(1), TLR4(10), TOLLIP(1), WNT1(1)	10111476	364	183	253	28	45	50	43	1	115	110	<1.00e-15	<2.68e-14
8	HSA04110_CELL_CYCLE	Genes involved in cell cycle	ABL1, ANAPC1, ANAPC10, ANAPC11, ANAPC2, ANAPC4, ANAPC5, ANAPC7, ATM, ATR, BUB1, BUB1B, BUB3, CCNA1, CCNA2, CCNB1, CCNB2, CCNB3, CCND1, CCND2, CCND3, CCNE1, CCNE2, CCNH, CDC14A, CDC14B, CDC16, CDC2, CDC20, CDC23, CDC25A, CDC25B, CDC25C, CDC26, CDC27, CDC45L, CDC6, CDC7, CDK2, CDK4, CDK6, CDK7, CDKN1A, CDKN1B, CDKN1C, CDKN2A, CDKN2B, CDKN2C, CDKN2D, CHEK1, CHEK2, CREBBP, CUL1, DBF4, E2F1, E2F2, E2F3, EP300, ESPL1, FZR1, GADD45A, GADD45B, GADD45G, GSK3B, hCG_1982709, HDAC1, HDAC2, LOC440917, LOC728919, MAD1L1, MAD2L1, MAD2L2, MCM2, MCM3, MCM4, MCM5, MCM6, MCM7, MDM2, ORC1L, ORC2L, ORC3L, ORC4L, ORC5L, ORC6L, PCNA, PKMYT1, PLK1, PRKDC, PTTG1, PTTG2, RB1, RBL1, RBL2, RBX1, SFN, SKP1, SKP2, SMAD2, SMAD3, SMAD4, SMC1A, SMC1B, TFDP1, TGFB1, TGFB2, TGFB3, TP53, WEE1, YWHAB, YWHAE, YWHAG, YWHAH, YWHAQ, YWHAZ	109	ABL1(4), ANAPC1(4), ANAPC10(2), ANAPC2(1), ANAPC4(4), ANAPC5(3), ANAPC7(4), ATM(39), ATR(18), BUB1(6), BUB1B(6), BUB3(2), CCNA1(6), CCNA2(3), CCNB1(2), CCNB2(2), CCNB3(7), CCND2(1), CCND3(1), CCNE1(3), CCNE2(2), CCNH(2), CDC14A(4), CDC14B(4), CDC16(4), CDC20(3), CDC23(6), CDC25A(2), CDC25B(5), CDC25C(4), CDC27(13), CDC6(1), CDC7(3), CDK2(2), CDK4(3), CDK6(1), CDK7(1), CDKN1A(1), CDKN1B(3), CDKN2C(1), CHEK1(1), CHEK2(1), CREBBP(25), CUL1(9), DBF4(5), E2F2(1), E2F3(2), EP300(15), ESPL1(8), GSK3B(8), HDAC1(2), HDAC2(2), MAD1L1(2), MAD2L1(1), MAD2L2(1), MCM3(4), MCM4(4), MCM5(6), MCM6(4), MCM7(3), MDM2(4), ORC1L(1), ORC3L(1), ORC4L(1), ORC5L(1), PCNA(3), PKMYT1(1), PLK1(9), PRKDC(18), PTTG1(1), RB1(8), RBL1(5), RBL2(8), RBX1(1), SKP1(1), SKP2(1), SMAD2(16), SMAD3(9), SMAD4(30), SMC1A(10), SMC1B(6), TFDP1(4), TGFB1(1), TGFB2(9), TP53(122), WEE1(3), YWHAB(2), YWHAE(3), YWHAH(1), YWHAQ(2)	46359792	569	183	495	106	172	161	112	9	105	10	<1.00e-15	<2.68e-14
9	PITX2PATHWAY	The bicoid-related transcription factor Pitx2 is activated by Wnt binding to the Frizzled receptor and induces tissue-specific cell proliferation.	APC, AXIN1, CREBBP, CTNNB1, DVL1, EP300, FZD1, GSK3B, HDAC1, HTATIP, LDB1, LEF1, PITX2, PPARBP, TRRAP, WNT1	14	APC(241), AXIN1(2), CREBBP(25), CTNNB1(12), EP300(15), FZD1(1), GSK3B(8), HDAC1(2), LDB1(5), LEF1(4), PITX2(2), TRRAP(21), WNT1(1)	10969528	339	180	248	31	46	36	32	2	117	106	<1.00e-15	<2.68e-14
10	ST_MYOCYTE_AD_PATHWAY	Cardiac myocytes have a variety of adrenergic receptors that induce subtype-specific signaling effects.	ADRB1, AKT1, APC, ASAH1, BF, CAMP, CAV3, DAG1, DLG4, EPHB2, GAS, GNAI1, GNAQ, HTATIP, ITPR1, ITPR2, ITPR3, KCNJ3, KCNJ5, KCNJ9, MAPK1, PITX2, PLB, PTX1, PTX3, RAC1, RHO, RYR1	23	ADRB1(3), AKT1(2), APC(241), ASAH1(3), CAV3(3), DAG1(5), DLG4(3), EPHB2(8), GNAI1(4), GNAQ(4), ITPR1(19), ITPR2(19), ITPR3(12), KCNJ3(6), KCNJ5(4), KCNJ9(3), MAPK1(2), PITX2(2), PTX3(2), RHO(3), RYR1(25)	15764424	373	180	282	59	69	53	28	0	115	108	<1.00e-15	<2.68e-14

Table 7. Get Full Table A Ranked List of Significantly Mutated Genesets (Excluding Significantly Mutated Genes). Number of significant genesets found: 44. Number of genesets displayed: 10

rank	geneset	description	genes	N_genes	mut_tally	N	n	npat	nsite	nsil	n1	n2	n3	n4	n5	n6	p	q
1	HSA04510_FOCAL_ADHESION	Genes involved in focal adhesion	ACTB, ACTG1, ACTN1, ACTN2, ACTN3, ACTN4, AKT1, AKT2, AKT3, ARHGAP5, BAD, BCAR1, BCL2, BIRC2, BIRC3, BIRC4, BRAF, CAPN2, CAV1, CAV2, CAV3, CCND1, CCND2, CCND3, CDC42, CHAD, COL11A1, COL11A2, COL1A1, COL1A2, COL2A1, COL3A1, COL4A1, COL4A2, COL4A4, COL4A6, COL5A1, COL5A2, COL5A3, COL6A1, COL6A2, COL6A3, COL6A6, COMP, CRK, CRKL, CTNNB1, DIAPH1, DOCK1, EGF, EGFR, ELK1, ERBB2, FARP2, FIGF, FLNA, FLNB, FLNC, FLT1, FN1, FYN, GRB2, GRLF1, GSK3B, HGF, HRAS, IBSP, IGF1, IGF1R, ILK, ITGA1, ITGA10, ITGA11, ITGA2, ITGA2B, ITGA3, ITGA4, ITGA5, ITGA6, ITGA7, ITGA8, ITGA9, ITGAV, ITGB1, ITGB3, ITGB4, ITGB5, ITGB6, ITGB7, ITGB8, JUN, KDR, LAMA1, LAMA2, LAMA3, LAMA4, LAMA5, LAMB1, LAMB2, LAMB3, LAMB4, LAMC1, LAMC2, LAMC3, LOC653852, MAP2K1, MAPK1, MAPK10, MAPK3, MAPK8, MAPK9, MET, MLCK, MRCL3, MRLC2, MYL2, MYL5, MYL7, MYL8P, MYL9, MYLC2PL, MYLK, MYLK2, MYLPF, PAK1, PAK2, PAK3, PAK4, PAK6, PAK7, PARVA, PARVB, PARVG, PDGFA, PDGFB, PDGFC, PDGFD, PDGFRA, PDGFRB, PDPK1, PGF, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, PIP5K1C, PPP1CA, PPP1CB, PPP1CC, PPP1R12A, PRKCA, PRKCB1, PRKCG, PTEN, PTK2, PXN, RAC1, RAC2, RAC3, RAF1, RAP1A, RAP1B, RAPGEF1, RELN, RHOA, ROCK1, ROCK2, SHC1, SHC2, SHC3, SHC4, SOS1, SOS2, SPP1, SRC, THBS1, THBS2, THBS3, THBS4, TLN1, TLN2, TNC, TNN, TNR, TNXB, VASP, VAV1, VAV2, VAV3, VCL, VEGFA, VEGFB, VEGFC, VTN, VWF, ZYX	178	ACTB(2), ACTN1(5), ACTN2(8), ACTN3(3), ACTN4(3), AKT1(2), AKT2(6), AKT3(1), ARHGAP5(9), BAD(1), BCL2(1), BIRC2(4), BIRC3(7), CAPN2(7), CAV1(1), CAV2(1), CAV3(3), CCND2(1), CCND3(1), CDC42(1), CHAD(7), COL11A2(11), COL1A1(11), COL2A1(9), COL4A1(14), COL4A2(4), COL4A4(10), COL4A6(15), COL5A1(16), COL5A2(13), COL5A3(10), COL6A2(1), COL6A6(21), COMP(2), CRKL(2), DIAPH1(1), DOCK1(7), EGF(3), EGFR(12), ERBB2(10), FARP2(5), FIGF(2), FLNA(3), FLNB(16), FLNC(13), FLT1(13), FN1(22), FYN(5), GRB2(3), GRLF1(12), HGF(8), IBSP(3), IGF1(2), IGF1R(8), ITGA1(3), ITGA10(7), ITGA11(4), ITGA2(6), ITGA2B(4), ITGA3(4), ITGA4(8), ITGA5(7), ITGA6(4), ITGA7(6), ITGA8(8), ITGA9(6), ITGAV(5), ITGB1(6), ITGB3(9), ITGB4(3), ITGB5(6), ITGB6(6), ITGB7(4), ITGB8(5), KDR(10), LAMA1(24), LAMA2(25), LAMA3(18), LAMA4(11), LAMB1(8), LAMB2(5), LAMB3(9), LAMB4(16), LAMC1(11), LAMC2(10), LAMC3(8), MAP2K1(4), MAPK1(2), MAPK3(3), MAPK8(7), MAPK9(5), MET(5), MYL2(1), MYL7(1), MYL9(2), MYLK(14), MYLK2(3), PAK1(5), PAK2(3), PAK3(5), PAK6(1), PAK7(7), PARVA(1), PARVB(5), PARVG(3), PDGFA(1), PDGFC(3), PDGFD(3), PDGFRB(6), PDPK1(1), PGF(2), PIK3CB(2), PIK3CD(3), PIK3CG(14), PIK3R2(1), PIK3R3(4), PIK3R5(1), PIP5K1C(4), PPP1CB(2), PPP1CC(2), PPP1R12A(3), PRKCA(4), PRKCG(10), PTK2(6), RAF1(6), RAP1A(2), RAP1B(2), RAPGEF1(6), RELN(33), ROCK1(15), ROCK2(6), SHC1(3), SHC2(1), SHC3(1), SHC4(5), SOS1(7), SOS2(11), SPP1(1), SRC(3), THBS1(10), THBS2(15), THBS3(3), THBS4(2), TLN1(7), TLN2(9), TNC(16), TNN(17), TNXB(17), VASP(3), VAV1(13), VAV2(4), VAV3(12), VCL(2), VEGFA(2), VEGFB(2), VEGFC(6), VTN(6), VWF(15), ZYX(1)	114677792	1040	160	1023	403	379	344	189	11	115	2	9.3e-08	0.000057
2	HSA04360_AXON_GUIDANCE	Genes involved in axon guidance	ABL1, ABLIM1, ABLIM2, ABLIM3, ARHGEF12, CDC42, CDK5, CFL1, CFL2, CHP, CXCL12, CXCR4, DCC, DPYSL2, DPYSL5, EFNA1, EFNA2, EFNA3, EFNA4, EFNA5, EFNB1, EFNB2, EFNB3, EPHA1, EPHA2, EPHA3, EPHA4, EPHA5, EPHA6, EPHA7, EPHA8, EPHB1, EPHB2, EPHB3, EPHB4, EPHB6, FES, FYN, GNAI1, GNAI2, GNAI3, GSK3B, HRAS, ITGB1, KRAS, L1CAM, LIMK1, LIMK2, LRRC4C, MAPK1, MAPK3, MET, NCK1, NCK2, NFAT5, NFATC1, NFATC2, NFATC3, NFATC4, NGEF, NRAS, NRP1, NTN1, NTN2L, NTN4, NTNG1, PAK1, PAK2, PAK3, PAK4, PAK6, PAK7, PLXNA1, PLXNA2, PLXNA3, PLXNB1, PLXNB2, PLXNB3, PLXNC1, PPP3CA, PPP3CB, PPP3CC, PPP3R1, PPP3R2, PTK2, RAC1, RAC2, RAC3, RASA1, RGS3, RHOA, RHOD, RND1, ROBO1, ROBO2, ROBO3, ROCK1, ROCK2, SEMA3A, SEMA3B, SEMA3C, SEMA3D, SEMA3E, SEMA3F, SEMA3G, SEMA4A, SEMA4B, SEMA4C, SEMA4D, SEMA4F, SEMA4G, SEMA5A, SEMA5B, SEMA6A, SEMA6B, SEMA6C, SEMA6D, SEMA7A, SLIT1, SLIT2, SLIT3, SRGAP1, SRGAP2, SRGAP3, UNC5A, UNC5B, UNC5C, UNC5D	118	ABL1(4), ABLIM1(6), ABLIM2(4), ABLIM3(5), ARHGEF12(9), CDC42(1), CFL1(1), CXCL12(1), CXCR4(4), DCC(16), DPYSL2(5), DPYSL5(1), EFNA3(1), EFNA4(1), EFNA5(5), EFNB1(3), EFNB2(1), EFNB3(3), EPHA1(6), EPHA2(5), EPHA4(6), EPHA6(5), EPHA7(10), EPHA8(6), EPHB1(9), EPHB2(8), EPHB3(2), EPHB4(5), EPHB6(4), FYN(5), GNAI1(4), ITGB1(6), L1CAM(4), LIMK1(5), LIMK2(5), LRRC4C(8), MAPK1(2), MAPK3(3), MET(5), NCK1(1), NFAT5(5), NFATC1(2), NFATC2(6), NFATC3(5), NFATC4(5), NGEF(1), NRP1(1), NTN1(5), NTN4(6), NTNG1(4), PAK1(5), PAK2(3), PAK3(5), PAK6(1), PAK7(7), PLXNA1(2), PLXNA2(8), PLXNA3(4), PLXNB1(5), PLXNB2(2), PLXNB3(3), PLXNC1(9), PPP3CA(3), PPP3CB(5), PPP3CC(4), PPP3R1(1), PPP3R2(1), PTK2(6), RASA1(9), RGS3(10), RND1(1), ROBO2(18), ROBO3(5), ROCK1(15), ROCK2(6), SEMA3A(9), SEMA3B(1), SEMA3C(3), SEMA3E(9), SEMA3F(1), SEMA3G(4), SEMA4A(3), SEMA4B(2), SEMA4D(13), SEMA4F(9), SEMA4G(6), SEMA5A(8), SEMA5B(11), SEMA6A(2), SEMA6B(2), SEMA6C(4), SEMA6D(9), SEMA7A(2), SLIT1(11), SLIT2(15), SLIT3(9), SRGAP1(9), SRGAP2(3), SRGAP3(4), UNC5A(2), UNC5B(6), UNC5D(9)	61947596	529	121	518	171	221	147	81	6	74	0	1.1e-06	0.00033
3	HSA04060_CYTOKINE_CYTOKINE_RECEPTOR_INTERACTION	Genes involved in cytokine-cytokine receptor interaction	ACVR1, ACVR1B, ACVR2A, ACVR2B, AMH, AMHR2, BMP2, BMP7, BMPR1A, BMPR1B, BMPR2, CCL1, CCL11, CCL13, CCL14, CCL15, CCL16, CCL17, CCL18, CCL19, CCL2, CCL20, CCL21, CCL22, CCL23, CCL24, CCL25, CCL26, CCL27, CCL28, CCL3, CCL4, CCL5, CCL7, CCL8, CCR1, CCR2, CCR3, CCR4, CCR5, CCR6, CCR7, CCR8, CCR9, CD27, CD40, CD40LG, CD70, CLCF1, CNTF, CNTFR, CRLF2, CSF1, CSF1R, CSF2, CSF2RA, CSF2RB, CSF3, CSF3R, CTF1, CX3CL1, CX3CR1, CXCL1, CXCL10, CXCL11, CXCL12, CXCL13, CXCL14, CXCL16, CXCL2, CXCL3, CXCL5, CXCL6, CXCL9, CXCR3, CXCR4, CXCR6, EDA, EDA2R, EDAR, EGF, EGFR, EPO, EPOR, FAS, FASLG, FLJ78302, FLT1, FLT3, FLT3LG, FLT4, GDF5, GH1, GH2, GHR, HGF, IFNA1, IFNA10, IFNA13, IFNA14, IFNA16, IFNA17, IFNA2, IFNA21, IFNA4, IFNA5, IFNA6, IFNA7, IFNA8, IFNAR1, IFNAR2, IFNB1, IFNE1, IFNG, IFNGR1, IFNGR2, IFNK, IFNW1, IL10, IL10RA, IL10RB, IL11, IL11RA, IL12A, IL12B, IL12RB1, IL12RB2, IL13, IL13RA1, IL15, IL15RA, IL17A, IL17B, IL17RA, IL17RB, IL18, IL18R1, IL18RAP, IL19, IL1A, IL1B, IL1R1, IL1R2, IL1RAP, IL2, IL20, IL20RA, IL21, IL21R, IL22, IL22RA1, IL22RA2, IL23A, IL23R, IL24, IL25, IL26, IL28A, IL28B, IL28RA, IL29, IL2RA, IL2RB, IL2RG, IL3, IL3RA, IL4, IL4R, IL5, IL5RA, IL6, IL6R, IL6ST, IL7, IL7R, IL8, IL8RA, IL8RB, IL9, IL9R, INHBA, INHBB, INHBC, INHBE, KDR, KIT, KITLG, LEP, LEPR, LIF, LIFR, LOC728045, LTA, LTB, LTBR, MET, MPL, NGFR, OSM, OSMR, PDGFB, PDGFC, PDGFRA, PDGFRB, PF4, PF4V1, PLEKHO2, PPBP, PRL, PRLR, RELT, TGFB1, TGFB2, TGFB3, TGFBR1, TGFBR2, TNF, TNFRSF10A, TNFRSF10B, TNFRSF10C, TNFRSF10D, TNFRSF11A, TNFRSF11B, TNFRSF12A, TNFRSF13B, TNFRSF13C, TNFRSF14, TNFRSF17, TNFRSF18, TNFRSF19, TNFRSF1A, TNFRSF1B, TNFRSF21, TNFRSF25, TNFRSF4, TNFRSF6B, TNFRSF8, TNFRSF9, TNFSF10, TNFSF11, TNFSF12, TNFSF13, TNFSF13B, TNFSF14, TNFSF15, TNFSF18, TNFSF4, TNFSF8, TNFSF9, TPO, TSLP, VEGFA, VEGFB, VEGFC, XCL1, XCL2, XCR1	237	ACVR1(4), ACVR2B(5), AMHR2(2), BMP2(1), BMP7(6), BMPR1A(4), BMPR1B(10), CCL13(1), CCL15(1), CCL18(2), CCL22(1), CCL23(2), CCL27(3), CCL7(1), CCL8(1), CCR1(5), CCR3(4), CCR4(1), CCR5(1), CCR6(2), CCR7(3), CCR8(4), CCR9(6), CD27(3), CD40(1), CD40LG(6), CD70(5), CNTF(2), CNTFR(2), CSF1(2), CSF1R(3), CSF2RB(7), CSF3R(10), CX3CL1(1), CX3CR1(3), CXCL10(1), CXCL11(3), CXCL12(1), CXCL14(2), CXCL16(1), CXCL5(2), CXCL6(1), CXCL9(3), CXCR4(4), EDA(2), EDA2R(2), EDAR(3), EGF(3), EGFR(12), FAS(2), FASLG(1), FLT1(13), FLT3(5), FLT3LG(1), FLT4(5), GDF5(2), GH1(2), GH2(3), GHR(6), HGF(8), IFNA1(1), IFNA10(3), IFNA13(2), IFNA16(4), IFNA2(4), IFNA21(1), IFNA4(2), IFNA5(1), IFNA6(3), IFNA7(1), IFNA8(1), IFNAR1(3), IFNAR2(2), IFNB1(1), IFNG(1), IFNGR1(3), IFNGR2(2), IFNK(1), IL10(2), IL10RA(2), IL10RB(5), IL11(1), IL11RA(1), IL12A(1), IL12B(2), IL12RB1(2), IL12RB2(6), IL13(1), IL13RA1(2), IL15(2), IL15RA(1), IL17A(2), IL17RA(7), IL17RB(1), IL18RAP(4), IL19(1), IL1A(1), IL1B(1), IL1R1(4), IL1R2(7), IL1RAP(1), IL20(3), IL20RA(5), IL21(2), IL21R(5), IL22(2), IL22RA1(1), IL23R(3), IL24(2), IL25(1), IL26(3), IL28RA(3), IL2RA(2), IL2RB(2), IL3(3), IL4(3), IL4R(1), IL5RA(6), IL6(2), IL6R(3), IL6ST(3), IL7(2), IL7R(3), IL8(1), IL9(2), INHBB(1), INHBC(3), INHBE(1), KDR(10), KIT(8), KITLG(2), LEP(1), LEPR(9), LTB(1), LTBR(3), MET(5), MPL(2), NGFR(3), OSM(1), OSMR(6), PDGFC(3), PDGFRB(6), PLEKHO2(5), PRL(3), PRLR(4), RELT(2), TGFB1(1), TGFB2(9), TGFBR1(9), TNFRSF10A(3), TNFRSF10B(6), TNFRSF10D(1), TNFRSF11A(3), TNFRSF11B(4), TNFRSF13B(4), TNFRSF17(2), TNFRSF19(3), TNFRSF1A(1), TNFRSF21(5), TNFRSF4(1), TNFRSF8(2), TNFRSF9(3), TNFSF10(1), TNFSF11(1), TNFSF12(2), TNFSF13(2), TNFSF13B(1), TNFSF14(3), TNFSF15(3), TNFSF18(1), TNFSF4(1), TNFSF8(1), TPO(11), TSLP(3), VEGFA(2), VEGFB(2), VEGFC(6), XCL2(1), XCR1(1)	54332092	537	115	525	188	178	194	98	0	67	0	1.6e-06	0.00033
4	HSA04350_TGF_BETA_SIGNALING_PATHWAY	Genes involved in TGF-beta signaling pathway	ACVR1, ACVR1B, ACVR1C, ACVR2A, ACVR2B, ACVRL1, AMH, AMHR2, BMP2, BMP4, BMP5, BMP6, BMP7, BMP8A, BMP8B, BMPR1A, BMPR1B, BMPR2, CDKN2B, CHRD, COMP, CREBBP, CUL1, DCN, E2F4, E2F5, EP300, FST, GDF5, GDF6, GDF7, hCG_1982709, ID1, ID2, ID3, ID4, IFNG, INHBA, INHBB, INHBC, INHBE, LEFTY1, LEFTY2, LTBP1, MAPK1, MAPK3, MYC, NODAL, NOG, PITX2, PPP2CA, PPP2CB, PPP2R1A, PPP2R1B, PPP2R2A, PPP2R2B, PPP2R2C, RBL1, RBL2, RBX1, RHOA, ROCK1, ROCK2, RPS6KB1, RPS6KB2, SKP1, SMAD1, SMAD2, SMAD3, SMAD4, SMAD5, SMAD6, SMAD7, SMAD9, SMURF1, SMURF2, SP1, TFDP1, TGFB1, TGFB2, TGFB3, TGFBR1, TGFBR2, THBS1, THBS2, THBS3, THBS4, TNF, ZFYVE16, ZFYVE9	81	ACVR1(4), ACVR1C(3), ACVR2B(5), ACVRL1(4), AMHR2(2), BMP2(1), BMP4(2), BMP5(5), BMP6(3), BMP7(6), BMP8A(1), BMPR1A(4), BMPR1B(10), CHRD(5), COMP(2), CREBBP(25), CUL1(9), DCN(4), E2F4(1), E2F5(2), EP300(15), FST(3), GDF5(2), GDF6(3), IFNG(1), INHBB(1), INHBC(3), INHBE(1), LTBP1(9), MAPK1(2), MAPK3(3), NODAL(1), PITX2(2), PPP2CA(1), PPP2CB(2), PPP2R1A(5), PPP2R1B(2), PPP2R2A(1), PPP2R2B(3), PPP2R2C(4), RBL1(5), RBL2(8), RBX1(1), ROCK1(15), ROCK2(6), RPS6KB1(3), RPS6KB2(2), SKP1(1), SMAD1(2), SMAD3(9), SMAD5(1), SMAD9(3), SMURF1(3), SMURF2(2), SP1(2), TFDP1(4), TGFB1(1), TGFB2(9), TGFBR1(9), THBS1(10), THBS2(15), THBS3(3), THBS4(2), ZFYVE16(12), ZFYVE9(10)	30546432	300	89	295	108	108	96	55	1	40	0	0.000019	0.0023
5	GPCRDB_CLASS_A_RHODOPSIN_LIKE		ADORA1, ADORA2A, ADORA2B, ADORA3, ADRA1A, ADRA1B, ADRA1D, ADRA2A, ADRA2C, ADRB1, ADRB2, ADRB3, AGTR1, AGTR2, AGTRL1, AVPR1A, AVPR1B, AVPR2, BDKRB1, BDKRB2, BLR1, BRS3, C3AR1, C5R1, CCBP2, CCKAR, CCKBR, CCR1, CCR10, CCR2, CCR3, CCR4, CCR5, CCR6, CCR7, CCR8, CCR9, CCRL1, CCRL2, CHML, CHRM1, CHRM2, CHRM3, CHRM4, CHRM5, CMKLR1, CMKOR1, CNR1, CNR2, CX3CR1, CXCR3, CXCR4, DRD1, DRD2, DRD3, DRD4, DRD5, EDNRA, EDNRB, ELA3A, F2R, F2RL1, F2RL2, F2RL3, FPR1, FPRL1, FPRL2, FSHR, GALR1, GALR2, GALR3, GALT, GHSR, GNB2L1, GPR10, GPR147, GPR17, GPR173, GPR174, GPR23, GPR24, GPR27, GPR3, GPR30, GPR35, GPR37, GPR37L1, GPR4, GPR44, GPR50, GPR6, GPR63, GPR74, GPR77, GPR83, GPR85, GPR87, GPR92, GRPR, HCRTR1, HCRTR2, HRH1, HRH2, HRH3, HTR1A, HTR1B, HTR1D, HTR1E, HTR1F, HTR2A, HTR2B, HTR2C, HTR4, HTR5A, HTR6, HTR7, HTR7, LOC93164, IL8RA, IL8RB, LHCGR, LTB4R, MAS1, MC1R, MC3R, MC4R, MC5R, MLNR, MTNR1A, MTNR1B, NMBR, NMUR1, NMUR2, NPY1R, NPY2R, NPY5R, NPY6R, NTSR1, NTSR2, OPN1SW, OPN3, OPRD1, OPRK1, OPRL1, OPRM1, OR10A5, OR11A1, OR12D3, OR1C1, OR1F1, OR1Q1, OR2H1, OR5V1, OR5V1, OR12D3, OR7A5, OR7C1, OR8B8, OXTR, P2RY1, P2RY10, P2RY11, P2RY12, P2RY13, P2RY14, P2RY2, P2RY5, P2RY6, PPYR1, PTAFR, PTGDR, PTGER1, PTGER2, PTGER4, PTGFR, PTGIR, Rgr, RGR, RHO, RRH, SSTR1, SSTR2, SSTR3, SSTR4, SUCNR1, TBXA2R, TRHR	155	ADORA1(8), ADORA2A(5), ADORA2B(1), ADORA3(3), ADRA1A(5), ADRA1B(5), ADRA1D(2), ADRA2A(3), ADRB1(3), ADRB3(1), AGTR1(6), AGTR2(5), AVPR1A(4), AVPR1B(3), AVPR2(6), BDKRB2(3), BRS3(3), C3AR1(4), CCKAR(3), CCKBR(5), CCR1(5), CCR3(4), CCR4(1), CCR5(1), CCR6(2), CCR7(3), CCR8(4), CCR9(6), CCRL1(5), CHML(5), CHRM1(3), CHRM3(4), CHRM4(1), CHRM5(2), CMKLR1(3), CNR1(5), CX3CR1(3), CXCR4(4), DRD1(1), DRD2(5), DRD3(3), DRD5(6), EDNRA(4), F2R(1), F2RL1(1), F2RL2(3), FPR1(2), FSHR(7), GALR1(2), GALT(2), GHSR(5), GPR17(1), GPR173(2), GPR174(3), GPR37(7), GPR37L1(3), GPR4(1), GPR50(5), GPR6(6), GPR63(4), GPR77(2), GPR83(1), GPR85(1), GPR87(5), GRPR(3), HCRTR1(1), HCRTR2(1), HRH1(1), HRH2(4), HTR1A(5), HTR1B(6), HTR1D(2), HTR1F(2), HTR2A(3), HTR2B(1), HTR2C(8), HTR4(3), HTR5A(5), HTR7(7), LHCGR(4), LTB4R(1), MAS1(2), MC3R(1), MC4R(4), MC5R(7), MLNR(3), MTNR1B(3), NMUR1(4), NPY1R(4), NPY2R(5), NPY5R(2), NTSR1(1), NTSR2(5), OPN1SW(3), OPN3(1), OPRD1(1), OPRK1(5), OPRM1(3), OR12D3(4), OR1C1(3), OR1F1(2), OR2H1(4), OR5V1(3), OR7A5(3), OR8B8(3), OXTR(3), P2RY1(6), P2RY12(4), P2RY13(2), P2RY2(3), P2RY6(1), PPYR1(4), PTAFR(1), PTGDR(1), PTGER2(1), PTGFR(6), PTGIR(1), RGR(3), RHO(3), RRH(4), SSTR1(5), SSTR2(3), SSTR4(4), SUCNR1(2), TRHR(8)	37861988	420	115	418	147	165	144	77	3	31	0	0.000019	0.0023
6	RHOPATHWAY	RhoA is a G protein whose active form stabilizes actin structures such as focal adhesions and activates Rock1, which phosphorylates myosin light chains.	ACTR2, ACTR3, ARHA, ARHGAP1, ARHGAP4, ARHGAP5, ARHGAP6, ARHGEF1, ARHGEF11, ARHGEF5, ARPC1A, ARPC1B, ARPC2, ARPC3, ARPC4, BAIAP2, CFL1, DIAPH1, GSN, LIMK1, MYL2, MYLK, OPHN1, PFN1, PIP5K1A, PIP5K1B, PPP1R12B, ROCK1, SRC, TLN1, VCL	30	ACTR2(2), ACTR3(3), ARHGAP4(1), ARHGAP5(9), ARHGAP6(3), ARHGEF1(5), ARHGEF11(11), ARHGEF5(7), ARPC1A(5), ARPC1B(2), ARPC2(2), BAIAP2(2), CFL1(1), DIAPH1(1), LIMK1(5), MYL2(1), MYLK(14), OPHN1(7), PIP5K1A(3), PIP5K1B(2), PPP1R12B(9), ROCK1(15), SRC(3), TLN1(7), VCL(2)	15703444	122	63	120	36	40	32	24	2	24	0	0.000044	0.0044
7	HSA00230_PURINE_METABOLISM	Genes involved in purine metabolism	ADA, ADCY1, ADCY2, ADCY3, ADCY4, ADCY5, ADCY6, ADCY7, ADCY8, ADCY9, ADK, ADSL, ADSS, ADSSL1, AK1, AK2, AK3L1, AK5, AK7, ALLC, AMPD1, AMPD2, AMPD3, APRT, ATIC, CANT1, DCK, DGUOK, ECGF1, ENPP1, ENPP3, ENTPD1, ENTPD2, ENTPD3, ENTPD4, ENTPD5, ENTPD6, ENTPD8, FHIT, GART, GDA, GMPR, GMPR2, GMPS, GUCY1A2, GUCY1A3, GUCY1B3, GUCY2C, GUCY2D, GUCY2F, GUK1, HPRT1, IMPDH1, IMPDH2, ITPA, NME1, NME2, NME4, NME6, NME7, NP, NPR1, NPR2, NT5C, NT5C1A, NT5C1B, NT5C2, NT5C3, NT5E, NT5M, NUDT2, NUDT5, NUDT9, PAICS, PAPSS1, PAPSS2, PDE10A, PDE11A, PDE1A, PDE1C, PDE2A, PDE3B, PDE4A, PDE4B, PDE4C, PDE4D, PDE5A, PDE6D, PDE6G, PDE6H, PDE7A, PDE7B, PDE8A, PDE8B, PDE9A, PFAS, PKLR, PKM2, PNPT1, POLA1, POLA2, POLD1, POLD2, POLD3, POLD4, POLE, POLE2, POLE3, POLE4, POLR1A, POLR1B, POLR1C, POLR1D, POLR2A, POLR2B, POLR2C, POLR2D, POLR2E, POLR2F, POLR2G, POLR2H, POLR2I, POLR2J, POLR2K, POLR2L, POLR3A, POLR3B, POLR3G, POLR3GL, POLR3H, POLR3K, PPAT, PRIM1, PRIM2, PRPS1, PRPS1L1, PRPS2, PRUNE, RFC5, RRM1, RRM2, RRM2B, SAC, XDH, ZNRD1	138	ADA(3), ADCY1(8), ADCY3(2), ADCY4(9), ADCY5(11), ADCY6(1), ADCY7(4), ADCY8(12), ADCY9(6), ADK(1), ADSL(7), ADSS(2), AK2(1), AK5(5), AK7(6), ALLC(5), AMPD1(9), AMPD2(5), AMPD3(3), ATIC(4), DCK(2), ENPP1(4), ENPP3(4), ENTPD1(2), ENTPD3(5), ENTPD4(5), ENTPD5(2), ENTPD6(3), FHIT(1), GART(3), GMPR(2), GMPR2(2), GMPS(5), GUCY1A2(12), GUCY1B3(9), GUCY2C(8), GUCY2D(8), GUCY2F(12), HPRT1(2), IMPDH1(2), IMPDH2(4), ITPA(2), NME6(4), NME7(5), NPR1(6), NPR2(10), NT5C1A(1), NT5C1B(10), NT5C2(4), NT5C3(2), NT5E(3), NT5M(1), NUDT9(2), PAICS(1), PAPSS1(2), PAPSS2(4), PDE11A(8), PDE1A(4), PDE1C(9), PDE3B(3), PDE4A(4), PDE4B(5), PDE4C(2), PDE4D(5), PDE5A(6), PDE6D(1), PDE7A(3), PDE7B(4), PDE8A(1), PDE8B(7), PDE9A(6), PFAS(1), PKM2(2), PNPT1(10), POLA1(8), POLA2(2), POLD1(5), POLD2(1), POLD3(2), POLE(21), POLE2(1), POLE3(1), POLR1A(11), POLR1B(9), POLR1C(2), POLR1D(2), POLR2A(6), POLR2B(8), POLR2D(1), POLR2E(1), POLR2H(1), POLR2I(1), POLR2K(1), POLR3A(11), POLR3B(11), POLR3GL(1), POLR3H(1), POLR3K(1), PPAT(6), PRPS1(1), PRPS1L1(1), PRPS2(2), PRUNE(1), RFC5(3), RRM1(2), RRM2(3), XDH(7)	53713612	474	109	467	151	162	161	84	2	65	0	5e-05	0.0044
8	HSA04630_JAK_STAT_SIGNALING_PATHWAY	Genes involved in Jak-STAT signaling pathway	AKT1, AKT2, AKT3, BCL2L1, CBL, CBLB, CBLC, CCND1, CCND2, CCND3, CISH, CLCF1, CNTF, CNTFR, CREBBP, CRLF2, CSF2, CSF2RA, CSF2RB, CSF3, CSF3R, CTF1, EP300, EPO, EPOR, GH1, GH2, GHR, GRB2, IFNA1, IFNA10, IFNA13, IFNA14, IFNA16, IFNA17, IFNA2, IFNA21, IFNA4, IFNA5, IFNA6, IFNA7, IFNA8, IFNAR1, IFNAR2, IFNB1, IFNE1, IFNG, IFNGR1, IFNGR2, IFNK, IFNW1, IL10, IL10RA, IL10RB, IL11, IL11RA, IL12A, IL12B, IL12RB1, IL12RB2, IL13, IL13RA1, IL13RA2, IL15, IL15RA, IL19, IL2, IL20, IL20RA, IL21, IL21R, IL22, IL22RA1, IL22RA2, IL23A, IL23R, IL24, IL26, IL28A, IL28B, IL28RA, IL29, IL2RA, IL2RB, IL2RG, IL3, IL3RA, IL4, IL4R, IL5, IL5RA, IL6, IL6R, IL6ST, IL7, IL7R, IL9, IL9R, IRF9, JAK1, JAK2, JAK3, LEP, LEPR, LIF, LIFR, MPL, MYC, OSM, OSMR, PIAS1, PIAS2, PIAS3, PIAS4, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, PIM1, PRL, PRLR, PTPN11, PTPN6, SOCS1, SOCS2, SOCS3, SOCS4, SOCS5, SOCS7, SOS1, SOS2, SPRED1, SPRED2, SPRY1, SPRY2, SPRY3, SPRY4, STAM, STAM2, STAT1, STAT2, STAT3, STAT4, STAT5A, STAT5B, STAT6, TPO, TSLP, TYK2	142	AKT1(2), AKT2(6), AKT3(1), BCL2L1(1), CBL(5), CBLB(8), CCND2(1), CCND3(1), CNTF(2), CNTFR(2), CREBBP(25), CSF2RB(7), CSF3R(10), EP300(15), GH1(2), GH2(3), GHR(6), GRB2(3), IFNA1(1), IFNA10(3), IFNA13(2), IFNA16(4), IFNA2(4), IFNA21(1), IFNA4(2), IFNA5(1), IFNA6(3), IFNA7(1), IFNA8(1), IFNAR1(3), IFNAR2(2), IFNB1(1), IFNG(1), IFNGR1(3), IFNGR2(2), IFNK(1), IL10(2), IL10RA(2), IL10RB(5), IL11(1), IL11RA(1), IL12A(1), IL12B(2), IL12RB1(2), IL12RB2(6), IL13(1), IL13RA1(2), IL13RA2(3), IL15(2), IL15RA(1), IL19(1), IL20(3), IL20RA(5), IL21(2), IL21R(5), IL22(2), IL22RA1(1), IL23R(3), IL24(2), IL26(3), IL28RA(3), IL2RA(2), IL2RB(2), IL3(3), IL4(3), IL4R(1), IL5RA(6), IL6(2), IL6R(3), IL6ST(3), IL7(2), IL7R(3), IL9(2), IRF9(3), JAK1(4), JAK2(11), JAK3(9), LEP(1), LEPR(9), MPL(2), OSM(1), OSMR(6), PIAS1(4), PIAS2(3), PIAS3(4), PIAS4(1), PIK3CB(2), PIK3CD(3), PIK3CG(14), PIK3R2(1), PIK3R3(4), PIK3R5(1), PIM1(1), PRL(3), PRLR(4), PTPN11(5), PTPN6(4), SOCS2(3), SOCS4(1), SOCS5(5), SOS1(7), SOS2(11), SPRED1(7), SPRED2(6), SPRY1(3), SPRY4(2), STAM(2), STAM2(2), STAT1(6), STAT2(7), STAT3(2), STAT4(3), STAT5B(3), STAT6(2), TPO(11), TSLP(3), TYK2(1)	45718076	416	99	408	130	143	146	76	1	46	4	0.000085	0.0059
9	HSA00240_PYRIMIDINE_METABOLISM	Genes involved in pyrimidine metabolism	AICDA, AK3, CAD, CANT1, CDA, CMPK, CTPS, CTPS2, DCK, DCTD, DHODH, DPYD, DPYS, DTYMK, DUT, ECGF1, ENTPD1, ENTPD3, ENTPD4, ENTPD5, ENTPD6, ENTPD8, ITPA, NME1, NME2, NME4, NME6, NME7, NP, NT5C, NT5C1A, NT5C1B, NT5C2, NT5C3, NT5E, NT5M, NUDT2, PNPT1, POLA1, POLA2, POLD1, POLD2, POLD3, POLD4, POLE, POLE2, POLE3, POLE4, POLR1A, POLR1B, POLR1C, POLR1D, POLR2A, POLR2B, POLR2C, POLR2D, POLR2E, POLR2F, POLR2G, POLR2H, POLR2I, POLR2J, POLR2K, POLR2L, POLR3A, POLR3B, POLR3G, POLR3GL, POLR3H, POLR3K, PRIM1, PRIM2, RFC5, RRM1, RRM2, RRM2B, TK1, TK2, TXNRD1, TXNRD2, TYMS, UCK1, UCK2, UMPS, UPB1, UPP1, UPP2, UPRT, ZNRD1	84	AICDA(4), AK3(1), CAD(12), CDA(1), CTPS(4), CTPS2(4), DCK(2), DCTD(3), DHODH(4), DPYS(7), DTYMK(1), ENTPD1(2), ENTPD3(5), ENTPD4(5), ENTPD5(2), ENTPD6(3), ITPA(2), NME6(4), NME7(5), NT5C1A(1), NT5C1B(10), NT5C2(4), NT5C3(2), NT5E(3), NT5M(1), PNPT1(10), POLA1(8), POLA2(2), POLD1(5), POLD2(1), POLD3(2), POLE(21), POLE2(1), POLE3(1), POLR1A(11), POLR1B(9), POLR1C(2), POLR1D(2), POLR2A(6), POLR2B(8), POLR2D(1), POLR2E(1), POLR2H(1), POLR2I(1), POLR2K(1), POLR3A(11), POLR3B(11), POLR3GL(1), POLR3H(1), POLR3K(1), RFC5(3), RRM1(2), RRM2(3), TK1(1), TK2(1), TXNRD1(3), TXNRD2(3), TYMS(3), UCK2(1), UMPS(1), UPB1(5), UPP2(2), UPRT(4)	26661776	243	78	239	58	71	91	51	1	29	0	0.000094	0.0059
10	MYOSINPATHWAY	Myosin light chain kinase phosphorylates myosin and promotes muscle contraction and platelet formation; myosin phosphatase antagonizes these processes.	ARHGAP5, ARHGEF1, GNA12, GNA13, GNAQ, GNB1, GNGT1, MYL2, MYLK, PLCB1, PPP1R12B, PRKCA, PRKCB1, PRKCL1, ROCK1	13	ARHGAP5(9), ARHGEF1(5), GNA12(2), GNA13(2), GNAQ(4), GNB1(1), GNGT1(1), MYL2(1), MYLK(14), PLCB1(8), PPP1R12B(9), PRKCA(4), ROCK1(15)	7003500	75	40	73	20	19	22	15	2	17	0	0.0001	0.0059

Methods & Data

Methods

In brief, we tabulate the number of mutations and the number of covered bases for each gene. The counts are broken down by mutation context category: four context categories that are discovered by MutSig, and one for indel and 'null' mutations, which include indels, nonsense mutations, splice-site mutations, and non-stop (read-through) mutations. For each gene, we calculate the probability of seeing the observed constellation of mutations, i.e. the product P1 x P2 x ... x Pm, or a more extreme one, given the background mutation rates calculated across the dataset.[1]

Download Results

This is an experimental feature. The full results of the analysis summarized in this report can be downloaded from the TCGA Data Coordination Center.

References

[1] TCGA, Integrated genomic analyses of ovarian carcinoma, Nature 474:609 � 615 (2011)