Acute Myeloid Leukemia: 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: LAML.

Number of patients in set: 199

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): 80

Mutations seen in COSMIC: 236

Significantly mutated genes in COSMIC territory: 18

Genes with clustered mutations (&le 3 aa apart): 30

Significantly mutated genesets: 73

Significantly mutated genesets: (excluding sig. mutated genes): 1

Results

Breakdown of Mutations by Type

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

type	count
Frame_Shift_Del	103
Frame_Shift_Ins	121
In_Frame_Del	100
In_Frame_Ins	58
Indel	4
Missense_Mutation	2725
Nonsense_Mutation	196
Nonstop_Mutation	2
Silent	1072
Splice_Site	104
Total	4485

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	801	275075312	2.9e-06	2.9	4.7
*Cp(A/C/T)->T	690	2493147819	2.8e-07	0.28	0.45
A->G	365	2773129874	1.3e-07	0.13	0.21
transver	869	5541353005	1.6e-07	0.16	0.25
indel+null	668	5541353204	1.2e-07	0.12	0.2
double_null	20	5541353204	3.6e-09	0.0036	0.0059
Total	3413	5541353204	6.2e-07	0.62	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: 80. Number of genes displayed: 35

rank	gene	description	N	n	npat	nsite	nsil	n1	n2	n3	n4	n5	n6	p	q
1	NPM1	nucleophosmin (nucleolar phosphoprotein B23, numatrin)	185269	47	47	1	0	0	0	0	0	47	0	1.4e-14	8.2e-11
2	FLT3	fms-related tyrosine kinase 3	603169	53	52	29	0	0	1	1	16	35	0	1.5e-14	8.2e-11
3	U2AF1	U2 small nuclear RNA auxiliary factor 1	154822	10	10	3	0	0	6	0	4	0	0	3.6e-14	8.2e-11
4	KRAS	v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog	140693	9	9	5	0	0	4	1	4	0	0	3.7e-14	8.2e-11
5	RUNX1	runt-related transcription factor 1 (acute myeloid leukemia 1; aml1 oncogene)	146663	20	17	16	0	1	3	2	3	9	2	3.9e-14	8.2e-11
6	TET2	tet oncogene family member 2	696898	22	15	22	0	0	1	0	2	9	10	4.3e-14	8.2e-11
7	WT1	Wilms tumor 1	166364	14	13	10	0	1	1	0	0	10	2	4.4e-14	8.2e-11
8	IDH1	isocitrate dehydrogenase 1 (NADP+), soluble	254123	20	20	2	0	18	0	0	2	0	0	4.6e-14	8.2e-11
9	TP53	tumor protein p53	260889	15	11	15	1	3	2	4	1	5	0	4.6e-14	8.2e-11
10	NRAS	neuroblastoma RAS viral (v-ras) oncogene homolog	116614	18	18	6	0	0	9	1	8	0	0	5e-14	8.2e-11
11	DNMT3A	DNA (cytosine-5-)-methyltransferase 3 alpha	517997	55	50	28	0	33	2	2	4	14	0	5.2e-14	8.2e-11
12	IDH2	isocitrate dehydrogenase 2 (NADP+), mitochondrial	232631	20	20	2	0	16	3	0	1	0	0	6.3e-14	9e-11
13	PHF6	PHD finger protein 6	246561	6	6	6	0	0	1	0	1	4	0	1.1e-12	1.4e-09
14	KIT	v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog	591229	8	7	5	0	1	0	0	5	2	0	5.4e-12	6.7e-09
15	PTPN11	protein tyrosine phosphatase, non-receptor type 11 (Noonan syndrome 1)	362976	7	7	6	0	0	3	1	3	0	0	1.8e-10	2.1e-07
16	ETV6	ets variant gene 6 (TEL oncogene)	276809	5	5	5	0	0	0	1	1	3	0	6.6e-10	7.2e-07
17	C17orf97		168553	5	5	4	1	0	0	1	4	0	0	6.1e-09	6.2e-06
18	MUC4	mucin 4, cell surface associated	1002562	10	7	8	6	1	0	1	5	3	0	1.2e-08	0.000012
19	SMC3	structural maintenance of chromosomes 3	746449	6	6	6	0	1	1	1	1	2	0	2.2e-08	2e-05
20	OR5H6	olfactory receptor, family 5, subfamily H, member 6	195418	4	4	1	2	0	0	0	0	4	0	2.3e-08	2e-05
21	AP3S1	adaptor-related protein complex 3, sigma 1 subunit	106067	3	3	1	0	0	0	0	0	3	0	3.2e-07	0.00027
22	SCRN3	secernin 3	259297	3	3	1	0	0	0	0	0	3	0	3.8e-07	0.00029
23	RAD21	RAD21 homolog (S. pombe)	387652	3	3	3	0	0	0	0	0	3	0	4.6e-07	0.00035
24	FAM5C	family with sequence similarity 5, member C	463471	6	5	6	0	4	1	0	1	0	0	6.1e-07	0.00044
25	NOTCH2NL	Notch homolog 2 (Drosophila) N-terminal like	144673	3	3	2	0	0	0	0	0	3	0	1e-06	0.0007
26	CYP21A2	cytochrome P450, family 21, subfamily A, polypeptide 2	205567	4	4	1	0	0	4	0	0	0	0	1.6e-06	0.0011
27	PRUNE2	prune homolog 2 (Drosophila)	1837964	7	6	4	0	2	0	0	0	3	2	1.7e-06	0.0011
28	NFKBIZ	nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, zeta	380488	3	3	1	0	0	0	0	0	3	0	2.5e-06	0.0015
29	MPRIP		375911	3	3	1	0	0	0	0	0	3	0	4.6e-06	0.0028
30	SMC1A	structural maintenance of chromosomes 1A	752419	5	5	5	0	1	0	1	2	1	0	5.7e-06	0.0033
31	ZNF275	zinc finger protein 275	193229	3	3	2	1	0	0	0	1	2	0	0.000011	0.0059
32	MAP3K4	mitogen-activated protein kinase kinase kinase 4	951021	4	4	2	0	0	0	1	0	3	0	0.000012	0.0066
33	TRIM48	tripartite motif-containing 48	128753	3	3	2	0	0	0	2	1	0	0	0.000013	0.0068
34	ASXL1	additional sex combs like 1 (Drosophila)	912415	5	5	5	0	0	0	0	0	5	0	0.000018	0.0092
35	C5orf25	chromosome 5 open reading frame 25	254123	3	3	2	0	1	2	0	0	0	0	0.000023	0.011

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)->T .

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

n4 - number of nonsilent mutations of type: transver .

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: 18. Number of genes displayed: 10

rank	gene	description	n	cos	n_cos	N_cos	cos_ev
1	IDH1	isocitrate dehydrogenase 1 (NADP+), soluble	20	3	20	597	29840
2	IDH2	isocitrate dehydrogenase 2 (NADP+), mitochondrial	20	6	20	1194	2000
3	NPM1	nucleophosmin (nucleolar phosphoprotein B23, numatrin)	47	29	47	5771	172819
4	NRAS	neuroblastoma RAS viral (v-ras) oncogene homolog	18	28	18	5572	13364
5	FLT3	fms-related tyrosine kinase 3	53	114	49	22686	6227
6	PTPN11	protein tyrosine phosphatase, non-receptor type 11 (Noonan syndrome 1)	7	31	6	6169	260
7	KRAS	v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog	9	51	8	10149	62973
8	RUNX1	runt-related transcription factor 1 (acute myeloid leukemia 1; aml1 oncogene)	20	175	18	34825	94
9	WT1	Wilms tumor 1	14	185	12	36815	612
10	KIT	v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog	8	183	7	36417	3934

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
659	DNMT3A	DNA (cytosine-5-)-methyltransferase 3 alpha	55	381	395
1037	IDH1	isocitrate dehydrogenase 1 (NADP+), soluble	20	190	190
1038	IDH2	isocitrate dehydrogenase 2 (NADP+), mitochondrial	20	139	139
836	FLT3	fms-related tyrosine kinase 3	53	120	136
1486	NRAS	neuroblastoma RAS viral (v-ras) oncogene homolog	18	81	81
1915	RUNX1	runt-related transcription factor 1 (acute myeloid leukemia 1; aml1 oncogene)	20	16	25
1169	KRAS	v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog	9	15	15
1155	KIT	v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog	8	10	10
1212	LILRA3	leukocyte immunoglobulin-like receptor, subfamily A (without TM domain), member 3	3	3	3
1787	PTPN11	protein tyrosine phosphatase, non-receptor type 11 (Noonan syndrome 1)	7	2	5

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: 73. Number of genesets displayed: 10

rank	geneset	description	genes	N_genes	mut_tally	N	n	npat	nsite	nsil	n1	n2	n3	n4	n5	p	q
1	ERYTHPATHWAY	Erythropoietin selectively stimulates erythrocyte differentiation from CFU-GEMM cells in bone marrow.	CCL3, CSF2, CSF3, EPO, FLT3, IGF1, IL11, IL1A, IL3, IL6, IL9, KITLG, TGFB1, TGFB2, TGFB3	14	FLT3(53), KITLG(1)	2401930	54	53	30	0	0	1	1	17	35	3.4e-15	4.1e-13
2	HSA04530_TIGHT_JUNCTION	Genes involved in tight junction	ACTB, ACTG1, ACTN1, ACTN2, ACTN3, ACTN4, AKT1, AKT2, AKT3, AMOTL1, ASH1L, CASK, CDC42, CDK4, CGN, CLDN1, CLDN10, CLDN11, CLDN14, CLDN15, CLDN16, CLDN17, CLDN18, CLDN19, CLDN2, CLDN20, CLDN22, CLDN23, CLDN3, CLDN4, CLDN5, CLDN6, CLDN7, CLDN8, CLDN9, CRB3, CSDA, CSNK2A1, CSNK2A2, CSNK2B, CTNNA1, CTNNA2, CTNNA3, CTNNB1, CTTN, EPB41, EPB41L1, EPB41L2, EPB41L3, EXOC3, EXOC4, F11R, GNAI1, GNAI2, GNAI3, HCLS1, HRAS, IGSF5, INADL, JAM2, JAM3, KRAS, LLGL1, LLGL2, MAGI1, MAGI2, MAGI3, MLLT4, MPDZ, MPP5, MRAS, MRCL3, MRLC2, MYH1, MYH10, MYH11, MYH13, MYH14, MYH15, MYH2, MYH3, MYH4, MYH6, MYH7, MYH7B, MYH8, MYH9, MYL2, MYL5, MYL7, MYL8P, MYL9, MYLC2PL, MYLPF, NRAS, OCLN, PARD3, PARD6A, PARD6B, PARD6G, PPM1J, PPP2CA, PPP2CB, PPP2R1A, PPP2R1B, PPP2R2A, PPP2R2B, PPP2R2C, PPP2R3A, PPP2R3B, PPP2R4, PRKCA, PRKCB1, PRKCD, PRKCE, PRKCG, PRKCH, PRKCI, PRKCQ, PRKCZ, PTEN, RAB13, RAB3B, RHOA, RRAS, RRAS2, SPTAN1, SRC, SYMPK, TJAP1, TJP1, TJP2, TJP3, VAPA, YES1, ZAK	126	CDC42(1), CGN(1), CLDN11(1), CLDN16(1), CLDN18(1), CTNNA2(1), EXOC4(1), GNAI2(1), HCLS1(1), IGSF5(1), JAM2(1), KRAS(9), LLGL2(1), MAGI1(1), MAGI2(1), MAGI3(1), MLLT4(2), MYH1(1), MYH13(2), MYH14(1), MYH15(1), MYH6(2), MYH7(2), MYL9(1), NRAS(18), PARD3(1), PPP2R1B(1), PPP2R2B(1), PPP2R3A(1), PRKCG(1), TJAP1(3), TJP1(1), TJP2(1)	55248171	64	51	47	13	12	19	6	22	5	7.1e-15	4.1e-13
3	GLUTATHIONE_METABOLISM		ANPEP, G6PD, GCLC, GCLM, GGT1, GPX1, GPX2, GPX3, GPX4, GPX5, GSS, GSTA1, GSTA2, GSTA3, GSTA4, GSTM1, GSTM2, GSTM3, GSTM4, GSTM5, GSTO2, GSTP1, GSTT1, GSTT2, GSTZ1, IDH1, IDH2, MGST1, MGST2, MGST3, PGD	29	G6PD(1), GCLM(1), GPX2(1), GSTM3(2), GSTT2(1), IDH1(20), IDH2(20), PGD(1)	5222954	47	45	11	1	34	7	1	5	0	7.1e-15	4.1e-13
4	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	242	ACVR2B(1), CCL11(1), CCL16(1), CCL17(1), CCL20(1), CCL21(1), CD70(1), CLCF1(1), CSF3R(2), CXCL16(1), EGF(1), EGFR(2), FLT1(1), FLT3(53), GHR(1), IFNA16(1), IL1R1(1), IL23R(1), IL25(1), KDR(2), KIT(8), KITLG(1), MPL(1), PDGFRA(1), PDGFRB(1), PLEKHO2(1), TPO(1)	50091285	89	80	62	10	7	10	3	31	38	8.7e-15	4.1e-13
5	HSA04012_ERBB_SIGNALING_PATHWAY	Genes involved in ErbB signaling pathway	ABL1, ABL2, AKT1, AKT2, AKT3, ARAF, AREG, BAD, BRAF, BTC, CAMK2A, CAMK2B, CAMK2D, CAMK2G, CBL, CBLB, CBLC, CDKN1A, CDKN1B, CRK, CRKL, EGF, EGFR, EIF4EBP1, ELK1, ERBB2, ERBB3, ERBB4, EREG, FRAP1, GAB1, GRB2, GSK3B, HBEGF, HRAS, JUN, KRAS, MAP2K1, MAP2K2, MAP2K4, MAP2K7, MAPK1, MAPK10, MAPK3, MAPK8, MAPK9, MYC, NCK1, NCK2, NRAS, NRG1, NRG2, NRG3, NRG4, PAK1, PAK2, PAK3, PAK4, PAK6, PAK7, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, PLCG1, PLCG2, PRKCA, PRKCB1, PRKCG, PTK2, RAF1, RPS6KB1, RPS6KB2, SHC1, SHC2, SHC3, SHC4, SOS1, SOS2, SRC, STAT5A, STAT5B, TGFA	82	ABL1(2), CBL(1), CBLC(1), CDKN1B(1), EGF(1), EGFR(2), ERBB3(2), KRAS(9), MAPK1(1), MYC(1), NRAS(18), PIK3CB(1), PIK3R2(1), PLCG2(1), PRKCG(1), RPS6KB2(2), SHC1(1), SOS1(1), STAT5B(1)	28520083	48	43	32	8	5	18	5	18	2	8.7e-15	4.1e-13
6	HSA00720_REDUCTIVE_CARBOXYLATE_CYCLE	Genes involved in reductive carboxylate cycle (CO2 fixation)	ACLY, ACO1, ACO2, ACSS1, ACSS2, FH, IDH1, IDH2, LOC441996, MDH1, MDH2, SUCLA2	11	ACO1(1), ACO2(1), IDH1(20), IDH2(20)	3905972	42	39	6	0	34	3	0	5	0	9.1e-15	4.1e-13
7	REDUCTIVE_CARBOXYLATE_CYCLE_CO2_FIXATION		ACO1, ACO2, FH, IDH1, IDH2, MDH1, MDH2, SDHB, SUCLA2	9	ACO1(1), ACO2(1), IDH1(20), IDH2(20)	2608293	42	39	6	0	34	3	0	5	0	9.8e-15	4.1e-13
8	HSA04640_HEMATOPOIETIC_CELL_LINEAGE	Genes involved in hematopoietic cell lineage	ANPEP, CD14, CD19, CD1A, CD1B, CD1C, CD1D, CD1E, CD2, CD22, CD24, CD33, CD34, CD36, CD37, CD38, CD3D, CD3E, CD3G, CD4, CD44, CD5, CD55, CD59, CD7, CD8A, CD8B, CD9, CR1, CR2, CSF1, CSF1R, CSF2, CSF2RA, CSF3, CSF3R, DNTT, EPO, EPOR, FCER2, FCGR1A, FLT3, FLT3LG, GP1BA, GP1BB, GP5, GP9, GYPA, HLA-DRA, HLA-DRB1, HLA-DRB3, HLA-DRB4, HLA-DRB5, IL11, IL11RA, IL1A, IL1B, IL1R1, IL1R2, IL2RA, IL3, IL3RA, IL4, IL4R, IL5, IL5RA, IL6, IL6R, IL7, IL7R, IL9R, ITGA1, ITGA2, ITGA2B, ITGA3, ITGA4, ITGA5, ITGA6, ITGAM, ITGB3, KIT, KITLG, MME, MS4A1, TFRC, THPO, TNF, TPO	83	CR1(1), CSF3R(2), FLT3(53), IL1R1(1), ITGA4(1), KIT(8), KITLG(1), MS4A1(1), TPO(1)	24232827	69	66	42	3	3	3	1	24	38	1e-14	4.1e-13
9	HSA00271_METHIONINE_METABOLISM	Genes involved in methionine metabolism	AHCY, AMD1, BHMT, CBS, CTH, DNMT1, DNMT3A, DNMT3B, KIAA0828, MARS, MARS2, MAT1A, MAT2B, MTAP, MTFMT, MTR, SRM, TAT	17	CBS(1), DNMT1(2), DNMT3A(55), DNMT3B(2), MAT1A(1)	5761050	61	54	34	0	35	2	4	6	14	1e-14	4.1e-13
10	HSA04540_GAP_JUNCTION	Genes involved in gap junction	ADCY1, ADCY2, ADCY3, ADCY4, ADCY5, ADCY6, ADCY7, ADCY8, ADCY9, ADRB1, CDC2, CSNK1D, DRD1, DRD2, EDG2, EGF, EGFR, GJA1, GJD2, GNA11, GNAI1, GNAI2, GNAI3, GNAQ, GNAS, GRB2, GRM1, GRM5, GUCY1A2, GUCY1A3, GUCY1B3, GUCY2C, GUCY2D, GUCY2F, HRAS, HTR2A, HTR2B, HTR2C, ITPR1, ITPR2, ITPR3, KRAS, LOC643224, LOC654264, MAP2K1, MAP2K2, MAP2K5, MAP3K2, MAPK1, MAPK3, MAPK7, NPR1, NPR2, NRAS, PDGFA, PDGFB, PDGFC, PDGFD, PDGFRA, PDGFRB, PLCB1, PLCB2, PLCB3, PLCB4, PRKACA, PRKACB, PRKACG, PRKCA, PRKCB1, PRKCG, PRKG1, PRKG2, PRKX, PRKY, RAF1, SOS1, SOS2, SRC, TJP1, TUBA1A, TUBA1B, TUBA1C, TUBA3C, TUBA3D, TUBA3E, TUBA4A, TUBA8, TUBAL3, TUBB, TUBB1, TUBB2A, TUBB2B, TUBB2C, TUBB3, TUBB4, TUBB4Q, TUBB6, TUBB8	90	ADCY2(1), ADCY3(1), ADCY4(2), ADCY5(1), DRD2(1), EGF(1), EGFR(2), GNAI2(1), GRM5(1), GUCY1B3(2), GUCY2C(1), GUCY2D(1), ITPR1(1), ITPR3(1), KRAS(9), MAPK1(1), NRAS(18), PDGFRA(1), PDGFRB(1), PLCB3(1), PRKCG(1), PRKG2(1), SOS1(1), TJP1(1), TUBA1A(1), TUBA1B(1), TUBA3C(2), TUBB3(1), TUBB4(1), TUBB6(1), TUBB8(1)	37538564	60	51	44	10	9	24	4	21	2	1e-14	4.1e-13

Table 7. Get Full Table A Ranked List of Significantly Mutated Genesets (Excluding Significantly Mutated Genes). Number of significant genesets found: 1. Number of genesets displayed: 10

rank	geneset	description	genes	N_genes	mut_tally	N	n	npat	nsite	nsil	n1	n2	n3	n4	n5	p	q
1	HSA04530_TIGHT_JUNCTION	Genes involved in tight junction	ACTB, ACTG1, ACTN1, ACTN2, ACTN3, ACTN4, AKT1, AKT2, AKT3, AMOTL1, ASH1L, CASK, CDC42, CDK4, CGN, CLDN1, CLDN10, CLDN11, CLDN14, CLDN15, CLDN16, CLDN17, CLDN18, CLDN19, CLDN2, CLDN20, CLDN22, CLDN23, CLDN3, CLDN4, CLDN5, CLDN6, CLDN7, CLDN8, CLDN9, CRB3, CSDA, CSNK2A1, CSNK2A2, CSNK2B, CTNNA1, CTNNA2, CTNNA3, CTNNB1, CTTN, EPB41, EPB41L1, EPB41L2, EPB41L3, EXOC3, EXOC4, F11R, GNAI1, GNAI2, GNAI3, HCLS1, HRAS, IGSF5, INADL, JAM2, JAM3, KRAS, LLGL1, LLGL2, MAGI1, MAGI2, MAGI3, MLLT4, MPDZ, MPP5, MRAS, MRCL3, MRLC2, MYH1, MYH10, MYH11, MYH13, MYH14, MYH15, MYH2, MYH3, MYH4, MYH6, MYH7, MYH7B, MYH8, MYH9, MYL2, MYL5, MYL7, MYL8P, MYL9, MYLC2PL, MYLPF, NRAS, OCLN, PARD3, PARD6A, PARD6B, PARD6G, PPM1J, PPP2CA, PPP2CB, PPP2R1A, PPP2R1B, PPP2R2A, PPP2R2B, PPP2R2C, PPP2R3A, PPP2R3B, PPP2R4, PRKCA, PRKCB1, PRKCD, PRKCE, PRKCG, PRKCH, PRKCI, PRKCQ, PRKCZ, PTEN, RAB13, RAB3B, RHOA, RRAS, RRAS2, SPTAN1, SRC, SYMPK, TJAP1, TJP1, TJP2, TJP3, VAPA, YES1, ZAK	124	CDC42(1), CGN(1), CLDN11(1), CLDN16(1), CLDN18(1), CTNNA2(1), EXOC4(1), GNAI2(1), HCLS1(1), IGSF5(1), JAM2(1), LLGL2(1), MAGI1(1), MAGI2(1), MAGI3(1), MLLT4(2), MYH1(1), MYH13(2), MYH14(1), MYH15(1), MYH6(2), MYH7(2), MYL9(1), PARD3(1), PPP2R1B(1), PPP2R2B(1), PPP2R3A(1), PRKCG(1), TJAP1(3), TJP1(1), TJP2(1)	54990864	37	31	36	13	12	6	4	10	5	0.000027	0.017
2	ERBB3PATHWAY	Neuregulins bind to the receptor tyrosine kinases ErbB3 and ErbB4, surface-localized receptors whose overexpression induces tumor formation.	EGF, EGFR, ERBB3, NRG1, UBE2D1	5	EGF(1), EGFR(2), ERBB3(2), UBE2D1(1)	2995149	6	6	6	1	1	1	0	3	1	0.00071	0.19
3	HSA05130_PATHOGENIC_ESCHERICHIA_COLI_INFECTION_EHEC	Genes involved in pathogenic Escherichia coli infection - EHEC	ABL1, ACTB, ACTG1, ARHGEF2, ARPC5, ARPC5L, CD14, CDC42, CDH1, CLDN1, CTNNB1, CTTN, EZR, FYN, HCLS1, ITGB1, KRT18, LOC643224, LOC654264, LY96, NCK1, NCK2, NCL, OCLN, PRKCA, RHOA, ROCK1, ROCK2, TLR4, TLR5, TUBA1A, TUBA1B, TUBA1C, TUBA3C, TUBA3D, TUBA3E, TUBA4A, TUBA8, TUBAL3, TUBB, TUBB1, TUBB2A, TUBB2B, TUBB2C, TUBB3, TUBB4, TUBB4Q, TUBB6, TUBB8, WAS, WASL, YWHAQ, YWHAZ	51	ABL1(2), CDC42(1), EZR(1), HCLS1(1), LY96(1), TLR4(1), TUBA1A(1), TUBA1B(1), TUBA3C(2), TUBB3(1), TUBB4(1), TUBB6(1), TUBB8(1), YWHAZ(1)	15524189	16	16	16	6	4	3	2	6	1	0.0012	0.19
4	HSA05131_PATHOGENIC_ESCHERICHIA_COLI_INFECTION_EPEC	Genes involved in pathogenic Escherichia coli infection - EPEC	ABL1, ACTB, ACTG1, ARHGEF2, ARPC5, ARPC5L, CD14, CDC42, CDH1, CLDN1, CTNNB1, CTTN, EZR, FYN, HCLS1, ITGB1, KRT18, LOC643224, LOC654264, LY96, NCK1, NCK2, NCL, OCLN, PRKCA, RHOA, ROCK1, ROCK2, TLR4, TLR5, TUBA1A, TUBA1B, TUBA1C, TUBA3C, TUBA3D, TUBA3E, TUBA4A, TUBA8, TUBAL3, TUBB, TUBB1, TUBB2A, TUBB2B, TUBB2C, TUBB3, TUBB4, TUBB4Q, TUBB6, TUBB8, WAS, WASL, YWHAQ, YWHAZ	51	ABL1(2), CDC42(1), EZR(1), HCLS1(1), LY96(1), TLR4(1), TUBA1A(1), TUBA1B(1), TUBA3C(2), TUBB3(1), TUBB4(1), TUBB6(1), TUBB8(1), YWHAZ(1)	15524189	16	16	16	6	4	3	2	6	1	0.0012	0.19
5	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	191	APC(4), ARHGEF1(1), ARHGEF6(1), BAIAP2(1), CDC42(1), DIAPH2(1), DOCK1(1), EGF(1), EGFR(2), EZR(1), FGF8(1), FN1(2), IQGAP3(3), ITGA10(1), ITGA11(1), ITGA4(1), ITGAD(2), ITGAV(1), ITGAX(1), ITGB2(1), MAPK1(1), MYH14(1), MYL9(1), MYLK(1), MYLK2(1), PDGFRA(1), PDGFRB(1), PIK3CB(1), PIK3R2(1), PIP5K1B(1), PIP5K1C(1), PPP1R12A(1), SOS1(1), SSH3(1), TIAM2(1), TMSL3(1), VAV3(1)	77184737	45	33	45	10	13	9	6	13	4	0.002	0.25
6	HSA04020_CALCIUM_SIGNALING_PATHWAY	Genes involved in calcium signaling pathway	ADCY1, ADCY2, ADCY3, ADCY4, ADCY7, ADCY8, ADCY9, ADORA2A, ADORA2B, ADRA1A, ADRA1B, ADRA1D, ADRB1, ADRB2, ADRB3, AGTR1, ATP2A1, ATP2A2, ATP2A3, ATP2B1, ATP2B2, ATP2B3, ATP2B4, AVPR1A, AVPR1B, BDKRB1, BDKRB2, BST1, CACNA1A, CACNA1B, CACNA1C, CACNA1D, CACNA1E, CACNA1F, CACNA1G, CACNA1H, CACNA1I, CACNA1S, CALM1, CALM2, CALM3, CALML3, CALML6, CAMK2A, CAMK2B, CAMK2D, CAMK2G, CAMK4, CCKAR, CCKBR, CD38, CHP, CHRM1, CHRM2, CHRM3, CHRM5, CHRNA7, CYSLTR1, CYSLTR2, DRD1, EDNRA, EDNRB, EGFR, ERBB2, ERBB3, ERBB4, F2R, GNA11, GNA14, GNA15, GNAL, GNAQ, GNAS, GRIN1, GRIN2A, GRIN2C, GRIN2D, GRM1, GRM5, GRPR, HRH1, HRH2, HTR2A, HTR2B, HTR2C, HTR4, HTR5A, HTR6, HTR7, ITPKA, ITPKB, ITPR1, ITPR2, ITPR3, LHCGR, LTB4R2, MLCK, MYLK, MYLK2, NOS1, NOS2A, NOS3, NTSR1, OXTR, P2RX1, P2RX2, P2RX3, P2RX4, P2RX5, P2RX7, P2RXL1, PDE1A, PDE1B, PDE1C, PDGFRA, PDGFRB, PHKA1, PHKA2, PHKB, PHKG1, PHKG2, PLCB1, PLCB2, PLCB3, PLCB4, PLCD1, PLCD3, PLCD4, PLCE1, PLCG1, PLCG2, PLCZ1, PLN, PPID, PPP3CA, PPP3CB, PPP3CC, PPP3R1, PPP3R2, PRKACA, PRKACB, PRKACG, PRKCA, PRKCB1, PRKCG, PRKX, PRKY, PTAFR, PTGER1, PTGER3, PTGFR, PTK2B, RYR1, RYR2, RYR3, SLC25A4, SLC25A5, SLC25A6, SLC8A1, SLC8A2, SLC8A3, SPHK1, SPHK2, TACR1, TACR2, TACR3, TBXA2R, TNNC1, TNNC2, TRHR, TRPC1, VDAC1, VDAC2, VDAC3	163	ADCY2(1), ADCY3(1), ADCY4(2), ADRA1A(1), ATP2A2(1), ATP2B2(1), ATP2B3(1), CACNA1B(3), CACNA1D(1), CACNA1E(3), CACNA1G(2), CACNA1I(1), CACNA1S(1), CAMK4(1), EGFR(2), ERBB3(2), GNA15(1), GRM5(1), HTR5A(1), ITPR1(1), ITPR3(1), MYLK(1), MYLK2(1), NOS1(1), P2RX7(1), PDGFRA(1), PDGFRB(1), PHKG1(1), PLCB3(1), PLCD4(1), PLCE1(4), PLCG2(1), PLCZ1(1), PPP3CA(1), PRKCG(1), PTK2B(1), RYR1(1), RYR3(4), TNNC2(1), TRPC1(1), VDAC1(1)	76549927	55	39	55	21	14	12	7	20	2	0.0084	0.8
7	HSA04080_NEUROACTIVE_LIGAND_RECEPTOR_INTERACTION	Genes involved in neuroactive ligand-receptor interaction	ADCYAP1R1, ADORA1, ADORA2A, ADORA2B, ADORA3, ADRA1A, ADRA1B, ADRA2A, ADRA2B, ADRA2C, ADRB1, ADRB2, ADRB3, AGTR1, AGTR2, AGTRL1, AVPR1A, AVPR1B, AVPR2, BDKRB1, BDKRB2, BRS3, C3AR1, C5AR1, CALCR, CALCRL, CCKAR, CCKBR, CGA, CHRM1, CHRM2, CHRM3, CHRM4, CHRM5, CNR1, CNR2, CRHR1, CRHR2, CTSG, CYSLTR1, CYSLTR2, DRD1, DRD2, DRD3, DRD4, DRD5, EDG1, EDG2, EDG3, EDG4, EDG5, EDG6, EDG7, EDG8, EDNRA, EDNRB, F2, F2R, F2RL1, F2RL2, F2RL3, FPR1, FPRL1, FPRL2, FSHB, FSHR, GABBR1, GABBR2, GABRA1, GABRA2, GABRA3, GABRA4, GABRA5, GABRA6, GABRB1, GABRB2, GABRB3, GABRD, GABRE, GABRG1, GABRG2, GABRG3, GABRP, GABRQ, GABRR1, GABRR2, GALR1, GALR2, GALR3, GCGR, GH1, GH2, GHR, GHRHR, GHSR, GIPR, GLP1R, GLP2R, GLRA1, GLRA2, GLRA3, GLRB, GNRHR, GPR156, GPR23, GPR35, GPR50, GPR63, GPR83, GRIA1, GRIA2, GRIA3, GRIA4, GRID1, GRID2, GRIK1, GRIK2, GRIK3, GRIK4, GRIK5, GRIN1, GRIN2A, GRIN2B, GRIN2C, GRIN2D, GRIN3A, GRIN3B, GRM1, GRM2, GRM3, GRM4, GRM5, GRM6, GRM7, GRM8, GRPR, GZMA, HCRTR1, HCRTR2, HRH1, HRH2, HRH3, HRH4, HTR1A, HTR1B, HTR1D, HTR1E, HTR1F, HTR2A, HTR2B, HTR2C, HTR4, HTR5A, HTR6, HTR7, KISS1R, LEP, LEPR, LHB, LHCGR, LTB4R, LTB4R2, MAS1, MC1R, MC2R, MC3R, MC4R, MC5R, MCHR1, MCHR2, MLNR, MTNR1A, MTNR1B, NMBR, NMUR1, NMUR2, NPBWR1, NPBWR2, NPFFR1, NPFFR2, NPY1R, NPY2R, NPY5R, NR3C1, NTSR1, NTSR2, OPRD1, OPRK1, OPRL1, OPRM1, OXTR, P2RX1, P2RX2, P2RX3, P2RX4, P2RX5, P2RX7, P2RXL1, P2RY1, P2RY10, P2RY11, P2RY13, P2RY14, P2RY2, P2RY4, P2RY5, P2RY6, P2RY8, PARD3, PPYR1, PRL, PRLHR, PRLR, PRSS1, PRSS2, PRSS3, PTAFR, PTGDR, PTGER1, PTGER2, PTGER3, PTGER4, PTGFR, PTGIR, PTH2R, PTHR1, RXFP1, RXFP2, SCTR, SSTR1, SSTR2, SSTR3, SSTR4, SSTR5, TAAR1, TAAR2, TAAR5, TAAR6, TAAR8, TAAR9, TACR1, TACR2, TACR3, TBXA2R, THRA, THRB, TRHR, TRPV1, TSHB, TSHR, TSPO, UTS2R, VIPR1, VIPR2	219	ADRA1A(1), BRS3(1), C5AR1(1), CRHR2(1), CTSG(1), DRD2(1), F2RL1(1), GABBR1(1), GABRA4(1), GABRB1(1), GABRG2(1), GABRR1(1), GHR(1), GLRA1(1), GNRHR(1), GPR156(1), GPR50(1), GRID1(2), GRIK2(3), GRIK3(2), GRIK4(3), GRIK5(1), GRIN3A(1), GRM3(2), GRM5(1), GRM6(2), GRM8(2), HTR5A(1), MCHR2(1), NTSR2(1), OPRM1(1), P2RX7(1), P2RY1(1), P2RY2(2), PARD3(1), PRSS3(1), SCTR(1), SSTR4(1), THRA(1), THRB(1), VIPR1(2)	60721467	52	39	52	16	16	17	3	13	3	0.0094	0.8
8	CLASSICPATHWAY	The classic complement pathway is initiated by antibodies and promotes phagocytosis and lysis of foreign cells as well as activating the inflammatory response.	C1QA, C1QB, C1QG, C1R, C1S, C2, C3, C4A, C4B, C5, C6, C7, C8A, C9	11	C1QA(1), C1S(1), C2(1), C3(1), C5(1), C7(1)	5144349	6	6	6	1	2	1	0	2	1	0.014	0.8
9	SA_CASPASE_CASCADE	Apoptosis is mediated by caspases, cysteine proteases arranged in a proteolytic cascade.	ADPRT, APAF1, BIRC2, BIRC3, BIRC4, CASP10, CASP3, CASP7, CASP8, CASP9, DFFA, DFFB, GZMB, PRF1, SCAP, SREBF1, SREBF2, TNFRSF6, TNFSF6	15	CASP10(1), CASP3(1), DFFA(1), DFFB(1), GZMB(1), SCAP(1), SREBF2(1)	4873112	7	6	7	1	1	4	0	2	0	0.014	0.8
10	HSA04540_GAP_JUNCTION	Genes involved in gap junction	ADCY1, ADCY2, ADCY3, ADCY4, ADCY5, ADCY6, ADCY7, ADCY8, ADCY9, ADRB1, CDC2, CSNK1D, DRD1, DRD2, EDG2, EGF, EGFR, GJA1, GJD2, GNA11, GNAI1, GNAI2, GNAI3, GNAQ, GNAS, GRB2, GRM1, GRM5, GUCY1A2, GUCY1A3, GUCY1B3, GUCY2C, GUCY2D, GUCY2F, HRAS, HTR2A, HTR2B, HTR2C, ITPR1, ITPR2, ITPR3, KRAS, LOC643224, LOC654264, MAP2K1, MAP2K2, MAP2K5, MAP3K2, MAPK1, MAPK3, MAPK7, NPR1, NPR2, NRAS, PDGFA, PDGFB, PDGFC, PDGFD, PDGFRA, PDGFRB, PLCB1, PLCB2, PLCB3, PLCB4, PRKACA, PRKACB, PRKACG, PRKCA, PRKCB1, PRKCG, PRKG1, PRKG2, PRKX, PRKY, RAF1, SOS1, SOS2, SRC, TJP1, TUBA1A, TUBA1B, TUBA1C, TUBA3C, TUBA3D, TUBA3E, TUBA4A, TUBA8, TUBAL3, TUBB, TUBB1, TUBB2A, TUBB2B, TUBB2C, TUBB3, TUBB4, TUBB4Q, TUBB6, TUBB8	88	ADCY2(1), ADCY3(1), ADCY4(2), ADCY5(1), DRD2(1), EGF(1), EGFR(2), GNAI2(1), GRM5(1), GUCY1B3(2), GUCY2C(1), GUCY2D(1), ITPR1(1), ITPR3(1), MAPK1(1), PDGFRA(1), PDGFRB(1), PLCB3(1), PRKCG(1), PRKG2(1), SOS1(1), TJP1(1), TUBA1A(1), TUBA1B(1), TUBA3C(2), TUBB3(1), TUBB4(1), TUBB6(1), TUBB8(1)	37281257	33	26	33	10	9	11	2	9	2	0.017	0.8

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)