Mutation Analysis (MutSig v2.0 and MutSigCV v0.9 merged result)

Uterine Corpus Endometrioid Carcinoma (Primary solid tumor)

15 January 2014 | analyses__2014_01_15

Maintainer Information

Citation Information

Maintained by Dan DiCara (Broad Institute)

Cite as Broad Institute TCGA Genome Data Analysis Center (2014): Mutation Analysis (MutSig v2.0 and MutSigCV v0.9 merged result). Broad Institute of MIT and Harvard. doi:10.7908/C15X27DZ

- Overview

+ Introduction

- Summary

MAF used for this analysis:UCEC-TP.final_analysis_set.maf
Significantly mutated genes (q ≤ 0.1): 28
Mutations seen in COSMIC: 995
Significantly mutated genes in COSMIC territory: 44
Significantly mutated genesets: 68

Mutation Preprocessing

Read 248 MAFs of type "WashU"
Total number of mutations in input MAFs: 184861
After removing 118 mutations outside chr1-24: 184743
After removing 1172 blacklisted mutations: 183571
After removing 1874 noncoding mutations: 181697
After collapsing adjacent/redundant mutations: 181695

Mutation Filtering

Number of mutations before filtering: 181695
After removing 15833 mutations outside gene set: 165862
After removing 1020 mutations outside category set: 164842
After removing 27 "impossible" mutations in
gene-patient-category bins of zero coverage: 147962

- Results

+ Breakdown of Mutations by Type

type	count
Frame_Shift_Del	952
Frame_Shift_Ins	419
In_Frame_Del	595
In_Frame_Ins	85
Missense_Mutation	110235
Nonsense_Mutation	11503
Nonstop_Mutation	126
Silent	38390
Splice_Site	2537
Total	164842

+ Breakdown of Mutation Rates by Category Type

category	n	N	rate	rate_per_mb	relative_rate	exp_ns_s_ratio
*CpG->T	37261	363920417	0.0001	100	5.6	2.2
*Cp(A/C/T)->mut	48789	3147487610	0.000016	16	0.85	3.4
A->mut	23124	3458111551	6.7e-06	6.7	0.37	3.8
*CpG->(G/A)	1045	363920417	2.9e-06	2.9	0.16	2.7
indel+null	15351	6969519578	2.2e-06	2.2	0.12	NaN
double_null	865	6969519578	1.2e-07	0.12	0.0068	NaN
Total	126435	6969519578	0.000018	18	1	3.5

+ Target Coverage for Each Individual

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

+ Lego Plots

+ CoMut Plot

+ Significantly Mutated Genes

Column Descriptions:

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
n6 = number of nonsilent mutations of type: double_null
p_cons = p-value for enrichment of mutations at evolutionarily most-conserved sites in gene
p_joint = p-value for clustering + conservation
p = p-value (overall)
q = q-value, False Discovery Rate (Benjamini-Hochberg procedure)

Table 3. Get Full Table A Ranked List of Significantly Mutated Genes. Number of significant genes found: 28. Number of genes displayed: 35. Click on a gene name to display its stick figure depicting the distribution of mutations and mutation types across the chosen gene (this feature may not be available for all significant genes).

rank	gene	description	N	n	npat	nsite	nsil	n1	n2	n3	n4	n5	n6	p_clust	p_cons	p_joint	p_cv	p	q
1	PPP2R1A	protein phosphatase 2 (formerly 2A), regulatory subunit A , alpha isoform	434902	30	27	18	3	10	17	1	0	2	0	0	0.14	0	8.8e-08	0	0
2	PIK3CA	phosphoinositide-3-kinase, catalytic, alpha polypeptide	813637	172	132	76	3	31	61	68	3	9	0	0	0	0	2.3e-15	0	0
3	CTNNB1	catenin (cadherin-associated protein), beta 1, 88kDa	592248	80	74	25	7	5	61	14	0	0	0	0	0	0	9.3e-15	0	0
4	PIK3R1	phosphoinositide-3-kinase, regulatory subunit 1 (alpha)	581125	100	83	77	2	4	4	13	1	63	15	0	0.44	0	8.9e-16	0	0
5	PRKAR1B	protein kinase, cAMP-dependent, regulatory, type I, beta	242642	4	4	4	3	2	0	0	1	1	0	0.0051	0	0	0.56	0	0
6	PTEN	phosphatase and tensin homolog (mutated in multiple advanced cancers 1)	306286	228	161	134	5	20	29	21	33	98	27	0	0.82	0	5.7e-15	0	0
7	KRAS	v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog	175322	53	53	11	2	1	47	4	1	0	0	0	0.00012	0	3e-12	0	0
8	TP53	tumor protein p53	317550	74	69	50	2	23	18	15	1	17	0	0	4e-07	0	1.3e-15	0	0
9	FBXW7	F-box and WD repeat domain containing 7	638720	46	39	30	1	22	12	2	1	8	1	0.0005	0.0086	0.00016	2.2e-14	1.1e-16	2.1e-13
10	CTCF	CCCTC-binding factor (zinc finger protein)	547098	48	44	38	1	8	4	7	0	26	3	0.012	0.08	0.022	5.2e-15	4.4e-15	7.4e-12
11	ARID1A	AT rich interactive domain 1A (SWI-like)	1412380	93	83	78	5	2	7	5	1	64	14	0.97	0.79	1	1.1e-15	3.9e-14	6e-11
12	SPOP	speckle-type POZ protein	287083	23	21	18	0	5	8	6	0	4	0	0.0034	0.035	0.0013	4.8e-09	1.7e-10	2.4e-07
13	ARID5B	AT rich interactive domain 5B (MRF1-like)	886908	34	29	34	8	5	5	8	2	13	1	0.064	0.96	0.15	9.4e-10	3.3e-09	4.2e-06
14	FGFR2	fibroblast growth factor receptor 2 (bacteria-expressed kinase, keratinocyte growth factor receptor, craniofacial dysostosis 1, Crouzon syndrome, Pfeiffer syndrome, Jackson-Weiss syndrome)	687457	34	31	19	3	3	5	13	9	3	1	0.022	0.3	0.045	9.1e-09	9.2e-09	0.000011
15	NFE2L2	nuclear factor (erythroid-derived 2)-like 2	446498	15	15	12	0	2	3	5	3	2	0	0.000085	0.031	0.000083	0.000091	1.5e-07	0.00017
16	CCND1	cyclin D1	154874	14	14	12	1	1	7	3	0	3	0	0.0009	0.15	0.0017	0.000014	4.2e-07	0.00044
17	CHD4	chromodomain helicase DNA binding protein 4	1452335	43	35	38	2	16	16	8	0	2	1	0.014	0.59	0.034	7.9e-07	4.9e-07	0.00049
18	FAM9A	family with sequence similarity 9, member A	249932	20	14	20	1	2	12	1	0	4	1	0.12	0.99	0.2	1.5e-06	4.9e-06	0.0046
19	MORC4	MORC family CW-type zinc finger 4	675031	28	20	26	2	6	10	1	0	11	0	0.69	0.23	0.65	5.7e-07	5.9e-06	0.0052
20	CASP8	caspase 8, apoptosis-related cysteine peptidase	434533	21	17	19	6	2	8	3	0	8	0	0.65	0.022	0.11	0.000014	0.000021	0.018
21	FOXA2	forkhead box A2	222670	13	12	13	1	1	3	3	0	6	0	0.1	0.23	0.16	0.000015	0.000033	0.027
22	ABI1	abl-interactor 1	390369	5	4	2	5	0	5	0	0	0	0	8e-07	1	2.8e-06	1	0.000039	0.029
23	DNER	delta/notch-like EGF repeat containing	485604	21	18	20	0	4	9	5	0	3	0	0.28	0.0024	0.0053	0.00061	0.000044	0.032
24	BCOR	BCL6 co-repressor	1283685	43	30	34	19	13	13	14	0	3	0	0.14	0.013	0.0077	0.00083	0.000082	0.057
25	BRS3	bombesin-like receptor 3	299754	17	15	17	2	1	11	1	0	4	0	0.14	0.17	0.2	0.000051	0.00013	0.086
26	SGK1	serum/glucocorticoid regulated kinase 1	469608	16	15	14	3	2	5	1	1	7	0	0.39	0.0069	0.03	0.00037	0.00014	0.089
27	NRAS	neuroblastoma RAS viral (v-ras) oncogene homolog	145328	9	9	6	2	1	4	3	0	1	0	0.08	0.015	0.014	0.00082	0.00014	0.089
28	TIAL1	TIA1 cytotoxic granule-associated RNA binding protein-like 1	297036	15	11	15	2	5	4	1	0	5	0	0.035	0.4	0.063	0.00019	0.00015	0.089
29	SIN3A	SIN3 homolog A, transcription regulator (yeast)	966485	29	21	27	3	5	7	7	0	10	0	0.026	0.067	0.016	0.0012	0.00024	0.14
30	SLC48A1	solute carrier family 48 (heme transporter), member 1	64852	5	5	5	0	1	2	1	0	1	0	0.7	0.87	1	0.000024	0.00028	0.16
31	RNF43	ring finger protein 43	573886	14	12	14	3	5	3	0	0	6	0	0.41	0.016	0.071	0.00041	0.00033	0.18
32	ZFHX3	zinc finger homeobox 3	2635180	79	44	71	13	30	20	6	1	22	0	0.043	0.23	0.048	0.00062	0.00034	0.18
33	RB1	retinoblastoma 1 (including osteosarcoma)	672795	26	20	25	4	7	6	5	0	5	3	0.55	0.39	0.61	0.000057	0.00039	0.2
34	NHSL2	NHS-like 2	753878	13	12	13	4	4	6	2	1	0	0	0.00081	0.001	0.000052	0.74	0.00044	0.21
35	CNPY1	canopy 1 homolog (zebrafish)	72047	8	7	7	0	3	0	2	0	3	0	0.07	0.34	0.11	0.00048	0.00056	0.27

+ 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: 44. Number of genes displayed: 10

rank	gene	description	n	cos	n_cos	N_cos	cos_ev	p	q
1	PTEN	phosphatase and tensin homolog (mutated in multiple advanced cancers 1)	228	767	219	190216	15125	0	0
2	PIK3R1	phosphoinositide-3-kinase, regulatory subunit 1 (alpha)	100	33	39	8184	111	2.6e-13	4.1e-10
3	FGFR2	fibroblast growth factor receptor 2 (bacteria-expressed kinase, keratinocyte growth factor receptor, craniofacial dysostosis 1, Crouzon syndrome, Pfeiffer syndrome, Jackson-Weiss syndrome)	34	51	24	12648	113	3.7e-13	4.1e-10
4	KRAS	v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog	53	52	49	12896	556649	3.8e-13	4.1e-10
5	FBXW7	F-box and WD repeat domain containing 7	46	91	29	22568	852	5.5e-13	4.1e-10
6	TP53	tumor protein p53	74	356	72	88288	24186	6.6e-13	4.1e-10
7	CTNNB1	catenin (cadherin-associated protein), beta 1, 88kDa	80	138	67	34224	23813	6.8e-13	4.1e-10
8	PIK3CA	phosphoinositide-3-kinase, catalytic, alpha polypeptide	172	220	150	54560	35669	7.5e-13	4.1e-10
9	NRAS	neuroblastoma RAS viral (v-ras) oncogene homolog	9	33	6	8184	6490	1.3e-08	6.3e-06
10	RB1	retinoblastoma 1 (including osteosarcoma)	26	267	11	66216	30	6.3e-08	0.000027

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)

+ Geneset Analyses

Table 5. Get Full Table A Ranked List of Significantly Mutated Genesets. (Source: MSigDB GSEA Cannonical Pathway Set).Number of significant genesets found: 68. 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_ns_s	p	q
1	EIF4PATHWAY	The eIF-4F complex recognizes 5' mRNA caps, recruits RNA helicases, and maintains mRNA-ribosome bridging.	AKT1, EIF4A1, EIF4A2, EIF4E, EIF4EBP1, EIF4G1, EIF4G2, EIF4G3, FRAP1, GHR, IRS1, MAPK1, MAPK14, MAPK3, MKNK1, PABPC1, PDK2, PDPK1, PIK3CA, PIK3R1, PRKCA, PRKCB1, PTEN, RPS6KB1	22	AKT1(4), EIF4A1(5), EIF4A2(9), EIF4E(2), EIF4G1(15), EIF4G2(7), EIF4G3(24), GHR(8), IRS1(13), MAPK1(2), MAPK14(4), MAPK3(3), MKNK1(3), PABPC1(10), PDK2(5), PDPK1(3), PIK3CA(172), PIK3R1(100), PRKCA(10), PTEN(228), RPS6KB1(5)	10144798	632	216	417	49	92	134	132	39	191	44	<1.00e-15	<1.00e-15	<4.76e-14
2	SA_PTEN_PATHWAY	PTEN is a tumor suppressor that dephosphorylates the lipid messenger phosphatidylinositol triphosphate.	AKT1, AKT2, AKT3, BPNT1, GRB2, ILK, MAPK1, MAPK3, PDK1, PIK3CA, PIK3CD, PIP3-E, PTEN, PTK2B, RBL2, SHC1, SOS1	16	AKT1(4), AKT2(6), AKT3(11), BPNT1(3), GRB2(3), ILK(5), MAPK1(2), MAPK3(3), PDK1(2), PIK3CA(172), PIK3CD(12), PTEN(228), PTK2B(16), RBL2(19), SHC1(7), SOS1(13)	7243620	506	208	307	39	92	126	107	36	117	28	<1.00e-15	<1.00e-15	<4.76e-14
3	SIG_IL4RECEPTOR_IN_B_LYPHOCYTES	Genes related to IL4 rceptor signaling in B lymphocytes	AKT1, AKT2, AKT3, BAD, BCL2, GRB2, GSK3A, GSK3B, IL4R, IRS1, IRS2, JAK1, JAK3, MAP4K1, MAPK1, MAPK3, PDK1, PIK3CA, PIK3CD, PIK3R1, PPP1R13B, RAF1, SHC1, SOCS1, SOS1, SOS2, STAT6	25	AKT1(4), AKT2(6), AKT3(11), BAD(2), GRB2(3), GSK3A(10), GSK3B(13), IL4R(6), IRS1(13), JAK1(20), JAK3(10), MAP4K1(11), MAPK1(2), MAPK3(3), PDK1(2), PIK3CA(172), PIK3CD(12), PIK3R1(100), PPP1R13B(9), RAF1(8), SHC1(7), SOS1(13), SOS2(17), STAT6(10)	12574116	464	202	337	55	106	123	119	5	95	16	9.87e-11	<1.00e-15	<4.76e-14
4	HCMVPATHWAY	Cytomegalovirus activates MAP kinase pathways in the host cell, inducing transcription of viral genes.	AKT1, CREB1, MAP2K1, MAP2K2, MAP2K3, MAP2K6, MAP3K1, MAPK1, MAPK14, MAPK3, NFKB1, PIK3CA, PIK3R1, RB1, RELA, SP1	16	AKT1(4), CREB1(6), MAP2K1(2), MAP2K2(5), MAP2K3(7), MAP2K6(10), MAP3K1(30), MAPK1(2), MAPK14(4), MAPK3(3), NFKB1(10), PIK3CA(172), PIK3R1(100), RB1(26), RELA(6), SP1(7)	7166136	394	200	272	31	63	112	107	4	89	19	2.19e-12	<1.00e-15	<4.76e-14
5	IL7PATHWAY	IL-7 is required for B and T cell development and proliferation and may contribute to activation of VDJ recombination.	BCL2, CREBBP, EP300, FYN, IL2RG, IL7, IL7R, JAK1, JAK3, LCK, NMI, PIK3CA, PIK3R1, PTK2B, STAT5A, STAT5B	16	CREBBP(32), EP300(32), FYN(7), IL2RG(13), IL7(1), IL7R(12), JAK1(20), JAK3(10), LCK(5), NMI(3), PIK3CA(172), PIK3R1(100), PTK2B(16), STAT5A(5), STAT5B(7)	10213532	435	200	312	56	77	121	115	6	100	16	3.60e-08	<1.00e-15	<4.76e-14
6	PAR1PATHWAY	Activated extracellular thrombin cleaves and activates the G-protein coupled receptors PAR1 and PAR4, which activate platelets.	ADCY1, ARHA, ARHGEF1, F2, F2R, F2RL3, GNA12, GNA13, GNAI1, GNAQ, GNB1, GNGT1, MAP3K7, PIK3CA, PIK3R1, PLCB1, PPP1R12B, PRKCA, PRKCB1, PTK2B, ROCK1	19	ADCY1(21), ARHGEF1(12), F2(8), F2R(6), GNA12(8), GNA13(7), GNAI1(5), GNAQ(3), GNB1(2), GNGT1(1), MAP3K7(9), PIK3CA(172), PIK3R1(100), PLCB1(5), PPP1R12B(20), PRKCA(10), PTK2B(16), ROCK1(22)	9289594	427	199	304	63	96	111	112	7	84	17	2.95e-06	<1.00e-15	<4.76e-14
7	ACHPATHWAY	Nicotinic acetylcholine receptors are ligand-gated ion channels that primarily mediate neuromuscular signaling and may inhibit neuronal apoptosis via the AKT pathway.	AKT1, BAD, CHRNB1, CHRNG, FOXO3A, MUSK, PIK3CA, PIK3R1, PTK2, PTK2B, RAPSN, SRC, TERT, TNFSF6, YWHAH	13	AKT1(4), BAD(2), CHRNB1(2), CHRNG(4), MUSK(15), PIK3CA(172), PIK3R1(100), PTK2(12), PTK2B(16), RAPSN(2), SRC(3), TERT(4), YWHAH(3)	5901003	339	197	220	43	57	93	94	4	76	15	2.46e-06	<1.00e-15	<4.76e-14
8	RASPATHWAY	Ras activation stimulates many signaling cascades, including PI3K/AKT activation to inhibit apoptosis.	AKT1, ARHA, BAD, BCL2L1, CASP9, CDC42, CHUK, ELK1, H2AFX, HRAS, MAP2K1, MAPK3, MLLT7, NFKB1, PIK3CA, PIK3R1, RAC1, RAF1, RALA, RALBP1, RALGDS, RELA, RHOA	21	AKT1(4), BAD(2), BCL2L1(4), CASP9(3), CDC42(4), CHUK(8), ELK1(3), H2AFX(1), HRAS(1), MAP2K1(2), MAPK3(3), NFKB1(10), PIK3CA(172), PIK3R1(100), RAC1(1), RAF1(8), RALA(6), RALBP1(6), RALGDS(9), RELA(6), RHOA(3)	6942603	356	197	235	28	56	106	95	4	78	17	4.18e-12	<1.00e-15	<4.76e-14
9	NKCELLSPATHWAY	Natural killer (NK) lymphocytes are inhibited by MHC and activated by surface glycoproteins on tumor or virus-infected cells, which undergo perforin-mediated lysis.	B2M, HLA-A, IL18, ITGB1, KLRC1, KLRC2, KLRC3, KLRC4, KLRD1, LAT, MAP2K1, MAPK3, PAK1, PIK3CA, PIK3R1, PTK2B, PTPN6, RAC1, SYK, VAV1	20	B2M(3), HLA-A(1), IL18(2), ITGB1(8), KLRC1(7), KLRC2(3), KLRC3(1), KLRC4(5), KLRD1(3), MAP2K1(2), MAPK3(3), PAK1(3), PIK3CA(172), PIK3R1(100), PTK2B(16), PTPN6(6), RAC1(1), SYK(4), VAV1(12)	6852023	352	196	232	34	59	99	93	5	81	15	2.61e-09	<1.00e-15	<4.76e-14
10	CTLA4PATHWAY	T cell activation requires interaction with an antigen-MHC-I complex on an antigen-presenting cell (APC), as well as CD28 interaction with the APC's CD80 or 86.	CD28, CD3D, CD3E, CD3G, CD3Z, CD80, CD86, CTLA4, GRB2, HLA-DRA, HLA-DRB1, ICOS, ICOSL, IL2, ITK, LCK, PIK3CA, PIK3R1, PTPN11, TRA@, TRB@	17	CD28(3), CD3D(6), CD3E(2), CD3G(3), CD80(5), CD86(5), CTLA4(2), GRB2(3), HLA-DRA(1), ICOS(3), IL2(2), ITK(7), LCK(5), PIK3CA(172), PIK3R1(100), PTPN11(8)	4602586	327	194	208	19	48	91	88	5	80	15	1.67e-12	<1.00e-15	<4.76e-14

+ Methods & Data

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