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

Bladder Urothelial Carcinoma (Primary solid tumor)

23 May 2013 | analyses__2013_05_23

Maintainer Information

Citation Information

Maintained by Dan DiCara (Broad Institute)

Cite as Broad Institute TCGA Genome Data Analysis Center (2013): Mutation Analysis (MutSig v2.0 and MutSigCV v0.9 merged result). Broad Institute of MIT and Harvard. doi:10.7908/C1DJ5CMT

- Overview

+ Introduction

- Summary

MAF used for this analysis:BLCA-TP.final_analysis_set.maf
Significantly mutated genes (q ≤ 0.1): 1
Mutations seen in COSMIC: 37
Significantly mutated genes in COSMIC territory: 3
Significantly mutated genesets: 21

Mutation Preprocessing

Read 28 MAFs of type "Broad"
Total number of mutations in input MAFs: 7557
After removing 3 mutations outside chr1-24: 7554
After removing 88 blacklisted mutations: 7466
After removing 140 noncoding mutations: 7326

Mutation Filtering

Number of mutations before filtering: 7326
After removing 93 mutations outside gene set: 7233
After removing 11 mutations outside category set: 7222

- Results

+ Breakdown of Mutations by Type

type	count
Frame_Shift_Del	94
Frame_Shift_Ins	39
In_Frame_Del	23
In_Frame_Ins	4
Missense_Mutation	4686
Nonsense_Mutation	418
Nonstop_Mutation	9
Silent	1826
Splice_Site	115
Translation_Start_Site	8
Total	7222

+ Breakdown of Mutation Rates by Category Type

category	n	N	rate	rate_per_mb	relative_rate	exp_ns_s_ratio
Tp*C->(T/G)	2636	108904258	0.000024	24	3.7	3
Tp*C->A	202	108904258	1.9e-06	1.9	0.28	4
(A/C/G)p*C->mut	1235	308289400	4e-06	4	0.61	3.2
A->mut	621	402887181	1.5e-06	1.5	0.23	3.9
indel+null	691	820080839	8.4e-07	0.84	0.13	NaN
double_null	11	820080839	1.3e-08	0.013	0.002	NaN
Total	5396	820080839	6.6e-06	6.6	1	3.5

+ Target Coverage for Each Individual

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

+ Needs description.

+ 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: Tp*C->(T/G)
n2 = number of nonsilent mutations of type: Tp*C->A
n3 = number of nonsilent mutations of type: (A/C/G)p*C->mut
n4 = number of nonsilent mutations of type: A->mut
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: 1. 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_cons	p_joint	p_cv	p	q
1	TP53	tumor protein p53	34506	14	11	13	1	2	0	8	1	3	0	0.0051	0.000022	0.0021	8.3e-07	0.015
2	FBXW7	F-box and WD repeat domain containing 7	68665	6	5	5	0	2	0	2	0	2	0	0.081	0.0033	0.0051	0.0002	1
3	TMCO2	transmembrane and coiled-coil domains 2	15596	2	2	1	0	0	0	0	0	2	0	0.9	0.15	0.0024	0.0032	1
4	NFE2L2	nuclear factor (erythroid-derived 2)-like 2	50092	4	4	4	0	1	0	1	2	0	0	0.011	0.022	0.047	0.008	1
5	AZI1	5-azacytidine induced 1	72929	3	2	3	2	3	0	0	0	0	0	0.014	0.0017	0.86	0.011	1
6	CRYBB1	crystallin, beta B1	21812	2	1	2	1	0	1	0	0	1	0	0.09	0.015	0.11	0.012	1
7	RFTN2	raftlin family member 2	40281	3	3	3	0	1	0	0	0	2	0	0.54	0.5	0.0049	0.017	1
8	H1FX	H1 histone family, member X	6847	2	1	2	0	2	0	0	0	0	0	0.19	0.038	0.07	0.019	1
9	GPS2	G protein pathway suppressor 2	26706	3	3	3	0	0	1	0	0	1	1	0.42	0.55	0.0059	0.022	1
10	PYGO1	pygopus homolog 1 (Drosophila)	35616	3	3	3	0	0	0	1	1	1	0	0.65	0.22	0.015	0.023	1
11	RPL31	ribosomal protein L31	12690	3	1	3	0	3	0	0	0	0	0	0.16	0.0065	0.57	0.024	1
12	TBCC	tubulin folding cofactor C	28768	3	1	3	0	3	0	0	0	0	0	0.005	0.0074	0.51	0.025	1
13	NXPH2	neurexophilin 2	20944	2	1	2	0	0	0	1	1	0	0	0.8	0.018	0.21	0.026	1
14	KLF5	Kruppel-like factor 5 (intestinal)	31500	2	2	2	1	0	0	0	0	2	0	0.42	0.4	0.0099	0.026	1
15	AMACR	alpha-methylacyl-CoA racemase	37197	2	2	2	0	1	0	0	0	1	0	0.23	0.063	0.064	0.026	1
16	ZNF263	zinc finger protein 263	58087	3	3	3	0	1	0	0	0	2	0	0.69	0.23	0.019	0.027	1
17	NUDT14	nudix (nucleoside diphosphate linked moiety X)-type motif 14	16739	1	1	1	0	0	0	0	0	1	0	NaN	NaN	0.03	0.03	1
18	C17orf81	chromosome 17 open reading frame 81	29954	3	2	3	1	2	0	1	0	0	0	0.096	0.011	0.43	0.031	1
19	MGA	MAX gene associated	241266	2	2	2	0	1	0	0	0	1	0	0.0048	0.0052	0.97	0.032	1
20	PLAUR	plasminogen activator, urokinase receptor	28994	3	2	3	0	3	0	0	0	0	0	0.4	0.014	0.38	0.033	1
21	LCE1F	late cornified envelope 1F	10079	1	1	1	0	0	0	0	0	1	0	NaN	NaN	0.033	0.033	1
22	CDH8	cadherin 8, type 2	68247	3	2	3	0	0	2	0	0	1	0	0.19	0.0063	0.88	0.034	1
23	FEZ2	fasciculation and elongation protein zeta 2 (zygin II)	22624	2	2	2	0	1	0	0	0	1	0	0.6	0.32	0.018	0.035	1
24	ADSS	adenylosuccinate synthase	37589	1	1	1	0	1	0	0	0	0	0	NaN	NaN	0.036	0.036	1
25	GINS1	GINS complex subunit 1 (Psf1 homolog)	17292	1	1	1	0	0	0	0	0	1	0	NaN	NaN	0.036	0.036	1
26	C11orf85	chromosome 11 open reading frame 85	19112	2	2	2	0	0	0	0	1	1	0	0.93	0.22	0.028	0.038	1
27	MGP	matrix Gla protein	8863	1	1	1	0	0	0	0	0	1	0	NaN	NaN	0.041	0.041	1
28	TP53I13	tumor protein p53 inducible protein 13	26129	1	1	1	0	0	0	0	0	1	0	NaN	NaN	0.041	0.041	1
29	NME4	non-metastatic cells 4, protein expressed in	13692	1	1	1	0	0	0	0	0	1	0	NaN	NaN	0.042	0.042	1
30	ELF3	E74-like factor 3 (ets domain transcription factor, epithelial-specific )	32054	3	3	3	0	0	0	1	0	2	0	0.52	1	0.0071	0.042	1
31	OR11H12	olfactory receptor, family 11, subfamily H, member 12	25197	1	1	1	0	0	0	0	0	1	0	NaN	NaN	0.042	0.042	1
32	TNFSF4	tumor necrosis factor (ligand) superfamily, member 4 (tax-transcriptionally activated glycoprotein 1, 34kDa)	15764	1	1	1	0	0	0	0	0	1	0	NaN	NaN	0.043	0.043	1
33	HLA-A	major histocompatibility complex, class I, A	29882	3	3	3	0	0	0	1	0	2	0	0.7	1	0.0072	0.043	1
34	INPP4B	inositol polyphosphate-4-phosphatase, type II, 105kDa	78653	2	1	2	0	0	0	1	0	1	0	0.03	0.02	0.37	0.044	1
35	XPR1	xenotropic and polytropic retrovirus receptor	59450	5	4	5	1	3	0	0	0	2	0	0.5	0.47	0.016	0.045	1

+ COSMIC analyses

rank	gene	description	n	cos	n_cos	N_cos	cos_ev	p	q
1	TP53	tumor protein p53	14	356	14	9968	2964	4.3e-13	1.9e-09
2	FBXW7	F-box and WD repeat domain containing 7	6	91	4	2548	102	3.2e-09	7.3e-06
3	FGFR3	fibroblast growth factor receptor 3 (achondroplasia, thanatophoric dwarfism)	2	62	2	1736	216	0.000065	0.098
4	DPYSL4	dihydropyrimidinase-like 4	1	1	1	28	2	0.00018	0.17
5	TBC1D8B	TBC1 domain family, member 8B (with GRAM domain)	2	1	1	28	1	0.00018	0.17
6	BMX	BMX non-receptor tyrosine kinase	2	2	1	56	2	0.00037	0.24
7	GABRA6	gamma-aminobutyric acid (GABA) A receptor, alpha 6	2	2	1	56	1	0.00037	0.24
8	BAZ1A	bromodomain adjacent to zinc finger domain, 1A	1	4	1	112	1	0.00074	0.32
9	PHIP	pleckstrin homology domain interacting protein	3	4	1	112	1	0.00074	0.32
10	SCN9A	sodium channel, voltage-gated, type IX, alpha subunit	1	4	1	112	1	0.00074	0.32

+ 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: 21. 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	TIDPATHWAY	On ligand binding, interferon gamma receptors stimulate JAK2 kinase to phosphorylate STAT transcription factors, which promote expression of interferon responsive genes.	DNAJA3, HSPA1A, IFNG, IFNGR1, IFNGR2, IKBKB, JAK2, LIN7A, NFKB1, NFKBIA, RB1, RELA, TIP-1, TNF, TNFRSF1A, TNFRSF1B, TP53, USH1C, WT1	18	IFNGR2(1), JAK2(1), RB1(2), RELA(1), TNFRSF1B(1), TP53(14), USH1C(1)	754587	21	15	19	1	5	1	9	1	4	1	0.023	2e-08	0.000012
2	PMLPATHWAY	Ring-shaped PML nuclear bodies regulate transcription and are required co-activators in p53- and DAXX-mediated apoptosis.	CREBBP, DAXX, HRAS, PAX3, PML, PRAM-1, RARA, RB1, SIRT1, SP100, TNF, TNFRSF1A, TNFRSF1B, TNFRSF6, TNFSF6, TP53, UBL1	13	CREBBP(5), DAXX(1), PML(3), RARA(2), RB1(2), SP100(1), TNFRSF1B(1), TP53(14)	792662	29	17	27	2	7	0	13	1	7	1	0.012	6e-08	0.000018
3	RNAPATHWAY	dsRNA-activated protein kinase phosphorylates elF2a, which generally inhibits translation, and activates NF-kB to provoke inflammation.	CHUK, DNAJC3, EIF2S1, EIF2S2, MAP3K14, NFKB1, NFKBIA, PRKR, RELA, TP53	9	DNAJC3(1), RELA(1), TP53(14)	408205	16	12	15	1	4	0	8	1	3	0	0.085	3.2e-07	0.000065
4	TERTPATHWAY	hTERC, the RNA subunit of telomerase, and hTERT, the catalytic protein subunit, are required for telomerase activity and are overexpressed in many cancers.	HDAC1, MAX, MYC, SP1, SP3, TP53, WT1, ZNF42	7	SP3(2), TP53(14)	292760	16	12	15	2	4	0	8	1	3	0	0.19	9.2e-07	0.00014
5	FBW7PATHWAY	Cyclin E interacts with cell cycle checkpoint kinase cdk2 to allow transcription of genes required for S phase, including transcription of additional cyclin E.	CCNE1, CDC34, CDK2, CUL1, E2F1, FBXW7, RB1, SKP1A, TFDP1	8	CUL1(4), FBXW7(6), RB1(2)	343289	12	9	9	0	5	0	3	0	3	1	0.06	5.9e-06	0.00072
6	RBPATHWAY	The ATM protein kinase recognizes DNA damage and blocks cell cycle progression by phosphorylating chk1 and p53, which normally inhibits Rb to allow G1/S transitions.	ATM, CDC2, CDC25A, CDC25B, CDC25C, CDK2, CDK4, CHEK1, MYT1, RB1, TP53, WEE1, YWHAH	12	ATM(3), RB1(2), TP53(14), WEE1(1)	734757	20	16	18	3	3	0	9	2	5	1	0.3	0.000026	0.0026
7	PLK3PATHWAY	Active Plk3 phosphorylates CDC25c, blocking the G2/M transition, and phosphorylates p53 to induce apoptosis.	ATM, ATR, CDC25C, CHEK1, CHEK2, CNK, TP53, YWHAH	7	ATM(3), ATR(3), TP53(14)	670310	20	13	19	2	6	0	9	2	3	0	0.18	0.000072	0.0064
8	SA_G1_AND_S_PHASES	Cdk2, 4, and 6 bind cyclin D in G1, while cdk2/cyclin E promotes the G1/S transition.	ARF1, ARF3, CCND1, CDK2, CDK4, CDKN1A, CDKN1B, CDKN2A, CFL1, E2F1, E2F2, MDM2, NXT1, PRB1, TP53	15	CCND1(1), CDKN1A(2), E2F2(1), TP53(14)	345627	18	12	17	3	4	0	9	2	3	0	0.22	0.00016	0.012
9	ARFPATHWAY	Cyclin-dependent kinase inhibitor 2A is a tumor suppressor that induces G1 arrest and can activate the p53 pathway, leading to G2/M arrest.	ABL1, CDKN2A, E2F1, MDM2, MYC, PIK3CA, PIK3R1, POLR1A, POLR1B, POLR1C, POLR1D, RAC1, RB1, TBX2, TP53, TWIST1	16	ABL1(1), PIK3CA(3), PIK3R1(1), RB1(2), TP53(14)	838723	21	13	19	3	5	1	9	1	4	1	0.16	0.00028	0.019
10	G1PATHWAY	CDK4/6-cyclin D and CDK2-cyclin E phosphorylate Rb, which allows the transcription of genes needed for the G1/S cell cycle transition.	ABL1, ATM, ATR, CCNA1, CCND1, CCNE1, CDC2, CDC25A, CDK2, CDK4, CDK6, CDKN1A, CDKN1B, CDKN2A, CDKN2B, DHFR, E2F1, GSK3B, HDAC1, MADH3, MADH4, RB1, SKP2, TFDP1, TGFB1, TGFB2, TGFB3, TP53	25	ABL1(1), ATM(3), ATR(3), CCND1(1), CDK6(1), CDKN1A(2), RB1(2), TP53(14)	1250337	27	17	25	3	10	0	10	2	4	1	0.079	0.0003	0.019

+ Methods & Data

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