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

Kidney Renal Papillary Cell 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/C1V40S7V

- Overview

+ Introduction

- Summary

MAF used for this analysis:KIRP-TP.final_analysis_set.maf
Significantly mutated genes (q ≤ 0.1): 5
Mutations seen in COSMIC: 43
Significantly mutated genes in COSMIC territory: 11
Significantly mutated genesets: 0

Mutation Preprocessing

Read 111 MAFs of type "Broad"
Total number of mutations in input MAFs: 10131
After removing 42 mutations outside chr1-24: 10089
After removing 348 blacklisted mutations: 9741
After removing 259 noncoding mutations: 9482
After collapsing adjacent/redundant mutations: 8036

Mutation Filtering

Number of mutations before filtering: 8036
After removing 124 mutations outside gene set: 7912
After removing 5 mutations outside category set: 7907

- Results

+ Breakdown of Mutations by Type

type	count
Frame_Shift_Del	528
Frame_Shift_Ins	201
In_Frame_Del	131
In_Frame_Ins	29
Missense_Mutation	4829
Nonsense_Mutation	266
Nonstop_Mutation	6
Silent	1725
Splice_Site	178
Translation_Start_Site	14
Total	7907

+ Breakdown of Mutation Rates by Category Type

category	n	N	rate	rate_per_mb	relative_rate	exp_ns_s_ratio
*CpG->T	511	184714396	2.8e-06	2.8	1.5	2.1
*Cp(A/C/T)->T	905	1496190153	6e-07	0.6	0.32	1.7
A->G	894	1608163559	5.6e-07	0.56	0.3	2.3
transver	2532	3289068108	7.7e-07	0.77	0.41	5
indel+null	1335	3289068108	4.1e-07	0.41	0.22	NaN
double_null	5	3289068108	1.5e-09	0.0015	0.00081	NaN
Total	6182	3289068108	1.9e-06	1.9	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: *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
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: 5. 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	p_cons	p_joint	p_cv	p	q
1	IL32	interleukin 32	61843	4	4	2	0	0	0	0	0	4	0.92	0.0002	1.8e-06	8e-09	0.00014
2	CDC27	cell division cycle 27 homolog (S. cerevisiae)	278169	4	4	1	0	0	0	0	0	4	0.083	4.8e-06	0.00055	5.5e-08	0.00049
3	NF2	neurofibromin 2 (merlin)	180272	7	7	7	0	0	0	0	0	7	0.97	0.68	1.1e-08	1.5e-07	0.00089
4	PPARGC1B	peroxisome proliferator-activated receptor gamma, coactivator 1 beta	317931	3	3	1	0	0	0	0	0	3	0.00046	0.000015	0.008	2.1e-06	0.0094
5	SFRS2IP	splicing factor, arginine/serine-rich 2, interacting protein	490729	5	5	2	1	0	0	0	1	4	0.0012	0.00012	0.0011	2.2e-06	0.0094
6	MET	met proto-oncogene (hepatocyte growth factor receptor)	474520	9	9	8	0	0	3	2	4	0	0.0016	0.000066	0.92	0.00065	1
7	ELF3	E74-like factor 3 (ets domain transcription factor, epithelial-specific )	126731	3	3	3	0	0	0	0	1	2	0.86	1	0.000097	0.00099	1
8	PCF11	PCF11, cleavage and polyadenylation factor subunit, homolog (S. cerevisiae)	472280	8	7	7	3	0	1	4	3	0	0.85	0.00066	0.21	0.0014	1
9	LGI4	leucine-rich repeat LGI family, member 4	78183	4	4	4	0	0	1	1	2	0	0.018	0.057	0.0029	0.0016	1
10	RAB27B	RAB27B, member RAS oncogene family	73617	1	1	1	0	0	0	0	0	1	NaN	NaN	0.0018	0.0018	1
11	STAG2	stromal antigen 2	432647	5	5	5	1	0	0	0	0	5	0.43	0.85	0.00025	0.002	1
12	PIPOX	pipecolic acid oxidase	133755	2	2	2	0	0	0	0	0	2	0.42	0.6	0.00053	0.0029	1
13	C6orf195	chromosome 6 open reading frame 195	43068	2	2	2	0	0	0	0	0	2	0.51	0.51	0.00081	0.0036	1
14	ACSBG2	acyl-CoA synthetase bubblegum family member 2	224342	3	3	1	0	0	0	0	3	0	1	0.0011	0.42	0.0041	1
15	BHMT	betaine-homocysteine methyltransferase	138466	4	4	4	0	0	0	3	0	1	0.1	0.22	0.0025	0.0046	1
16	LYAR	Ly1 antibody reactive homolog (mouse)	130092	2	2	2	0	1	0	0	0	1	0.12	0.037	0.021	0.0062	1
17	LHFPL4	lipoma HMGIC fusion partner-like 4	83748	1	1	1	0	0	0	0	0	1	NaN	NaN	0.0063	0.0063	1
18	POMC	proopiomelanocortin (adrenocorticotropin/ beta-lipotropin/ alpha-melanocyte stimulating hormone/ beta-melanocyte stimulating hormone/ beta-endorphin)	63547	3	3	3	0	1	0	0	1	1	0.54	0.4	0.002	0.0064	1
19	RPTN	repetin	262185	3	3	3	0	1	0	1	0	1	0.022	0.0034	0.24	0.0066	1
20	SAV1	salvador homolog 1 (Drosophila)	128652	3	3	3	0	0	1	0	0	2	0.98	0.18	0.0049	0.0072	1
21	NFE2L2	nuclear factor (erythroid-derived 2)-like 2	197785	3	3	3	0	0	0	1	2	0	0.013	0.0048	0.21	0.0079	1
22	IFNA16	interferon, alpha 16	63475	2	2	1	0	0	1	0	1	0	0.16	0.048	0.021	0.0079	1
23	PEBP1	phosphatidylethanolamine binding protein 1	48779	2	2	2	0	0	1	0	1	0	0.21	0.023	0.045	0.0082	1
24	MCCC2	methylcrotonoyl-Coenzyme A carboxylase 2 (beta)	180567	2	2	2	0	0	0	0	1	1	0.035	0.018	0.068	0.0096	1
25	POU4F2	POU class 4 homeobox 2	120647	2	2	1	0	0	0	0	0	2	0.99	0.18	0.0074	0.01	1
26	PARD6B	par-6 partitioning defective 6 homolog beta (C. elegans)	117771	4	4	4	0	0	0	2	0	2	0.74	0.98	0.0015	0.011	1
27	VPS37D	vacuolar protein sorting 37 homolog D (S. cerevisiae)	30362	1	1	1	0	0	0	0	0	1	NaN	NaN	0.011	0.011	1
28	STARD3	StAR-related lipid transfer (START) domain containing 3	152873	2	2	2	0	0	0	0	0	2	0.059	0.088	0.019	0.012	1
29	WFDC10A	WAP four-disulfide core domain 10A	27441	1	1	1	0	0	0	0	0	1	NaN	NaN	0.015	0.015	1
30	LRFN4	leucine rich repeat and fibronectin type III domain containing 4	130619	3	3	3	0	1	0	0	0	2	0.69	1	0.0022	0.016	1
31	TMEM37	transmembrane protein 37	61716	1	1	1	0	0	0	1	0	0	NaN	NaN	0.017	0.017	1
32	SEPT7	septin 7	96217	2	2	2	0	0	0	0	0	2	0.88	1	0.003	0.02	1
33	C10orf95	chromosome 10 open reading frame 95	29115	1	1	1	0	0	0	0	0	1	NaN	NaN	0.021	0.021	1
34	C15orf52	chromosome 15 open reading frame 52	156736	1	1	1	0	0	0	0	0	1	NaN	NaN	0.021	0.021	1
35	KDELR3	KDEL (Lys-Asp-Glu-Leu) endoplasmic reticulum protein retention receptor 3	80347	2	2	2	0	0	0	1	0	1	0.14	0.18	0.018	0.022	1

+ COSMIC analyses

rank	gene	description	n	cos	n_cos	N_cos	cos_ev	p	q
1	MET	met proto-oncogene (hepatocyte growth factor receptor)	9	34	4	3774	12	1e-10	4.7e-07
2	FGFR3	fibroblast growth factor receptor 3 (achondroplasia, thanatophoric dwarfism)	5	62	3	6882	1469	3.6e-07	0.00081
3	NF2	neurofibromin 2 (merlin)	7	550	4	61050	29	6.6e-06	0.0099
4	SMARCA4	SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4	5	30	2	3330	3	0.000019	0.022
5	KRAS	v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog	2	52	2	5772	29208	0.000058	0.053
6	BRAF	v-raf murine sarcoma viral oncogene homolog B1	4	89	2	9879	14380	0.00017	0.086
7	CDCA8	cell division cycle associated 8	1	1	1	111	1	0.00021	0.086
8	FLCN	folliculin	1	1	1	111	1	0.00021	0.086
9	G6PC	glucose-6-phosphatase, catalytic subunit	1	1	1	111	1	0.00021	0.086
10	PLXDC2	plexin domain containing 2	1	1	1	111	1	0.00021	0.086

+ 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: 0. Number of genesets displayed: 10

rank	geneset	description	genes	N_genes	mut_tally	N	n	npat	nsite	nsil	n1	n2	n3	n4	n5	p_ns_s	p	q
1	MTORPATHWAY	Mammalian target of rapamycin (mTOR) senses mitogenic factors and nutrients, including ATP, and induces cell proliferation.	AKT1, EIF3S10, EIF4A1, EIF4A2, EIF4B, EIF4E, EIF4EBP1, EIF4G1, EIF4G2, EIF4G3, FKBP1A, FRAP1, MKNK1, PDK2, PDPK1, PIK3CA, PIK3R1, PPP2CA, PTEN, RPS6, RPS6KB1, TSC1, TSC2	21	EIF4A1(1), EIF4B(2), EIF4G1(2), EIF4G3(4), PIK3CA(2), PIK3R1(1), PTEN(3), TSC1(2), TSC2(4)	4612682	21	19	21	2	2	6	3	3	7	0.047	0.0011	0.66
2	ALANINE_AND_ASPARTATE_METABOLISM		AARS, ABAT, ADSL, ADSS, AGXT, AGXT2, ASL, ASNS, ASPA, ASS, CAD, CRAT, DARS, DDO, GAD1, GAD2, GOT1, GOT2, GPT, GPT2, NARS, PC	21	AARS(1), ADSL(1), AGXT(1), AGXT2(1), ASNS(1), CAD(3), CRAT(1), DARS(3), DDO(1), GPT(2), PC(4)	4337938	19	17	19	1	0	3	1	8	7	0.078	0.0034	1
3	CBLPATHWAY	Activated EGF receptors undergo endocytosis into clathrin-coated vesicles, where they are recycled to the membrane or ubiquitinated by Cbl.	CBL, CSF1R, EGF, EGFR, GRB2, MET, PDGFRA, PRKCA, PRKCB1, SH3GLB1, SH3GLB2, SH3KBP1, SRC	12	CSF1R(1), EGF(1), MET(9), PDGFRA(2)	3225375	13	12	12	1	1	3	2	6	1	0.11	0.0074	1
4	NEUTROPHILPATHWAY	Neutrophils are phagocytotic leukocytes that destroy foreign cells with reactive oxygen species or enzymatic digestion and express CD11 and CD18.	CD44, ICAM1, ITGAL, ITGAM, ITGB2, PECAM1, SELE, SELL	8	ITGAL(3), ITGAM(2), ITGB2(1), SELE(1), SELL(1)	1726164	8	8	8	0	1	2	0	3	2	0.13	0.01	1
5	KREBPATHWAY	The Krebs (citric acid) cycle takes place in mitochondria, where it extracts energy in the form of electron carriers NADH and FADH2, which drive the electron transport chain.	ACO2, CS, FH, IDH2, MDH1, OGDH, SDHA, SUCLA2	8	FH(1), IDH2(1), MDH1(1), OGDH(2), SDHA(2)	1558671	7	7	7	0	0	3	0	1	3	0.072	0.01	1
6	LYMPHOCYTEPATHWAY	B and T cell lymphocytes interact with other cells via transmembrane adhesion proteins such as CD44, which interacts with endothelial cells.	CD44, ICAM1, ITGA4, ITGAL, ITGB1, ITGB2, PECAM1, SELE, SELL	9	ITGA4(1), ITGAL(3), ITGB1(1), ITGB2(1), SELE(1), SELL(1)	1999098	8	8	8	0	1	2	1	1	3	0.15	0.011	1
7	MONOCYTEPATHWAY	Monocytes are a class of immune phagocytes that can develop into macrophages and express LFA-1, CD44, and other surface signaling proteins.	CD44, ICAM1, ITGA4, ITGAL, ITGAM, ITGB1, ITGB2, PECAM1, SELE, SELL, SELP	11	ITGA4(1), ITGAL(3), ITGAM(2), ITGB1(1), ITGB2(1), SELE(1), SELL(1)	2640660	10	10	10	0	1	2	1	3	3	0.11	0.014	1
8	DNAFRAGMENTPATHWAY	DNA fragmentation during apoptosis is effected by DFF, a caspase-activated DNAse, and by endonuclease G.	CASP3, CASP7, DFFA, DFFB, ENDOG, GZMB, HMGB1, HMGB2, TOP2A, TOP2B	9	HMGB1(3), HMGB2(2), TOP2B(3)	1504641	8	7	8	0	1	1	1	3	2	0.21	0.016	1
9	HSA00830_RETINOL_METABOLISM	Genes involved in retinol metabolism	ALDH1A1, ALDH1A2, BCMO1, RDH5	4	BCMO1(2), RDH5(2)	643601	4	4	4	1	0	0	3	0	1	0.72	0.017	1
10	RABPATHWAY	Rab family GTPases regulate vesicle transport, endocytosis and exocytosis, and vesicle docking via interactions with the rabphilins.	ACTA1, MEL, RAB11A, RAB1A, RAB2, RAB27A, RAB3A, RAB4A, RAB5A, RAB6A, RAB7, RAB9A	9	ACTA1(1), RAB11A(1), RAB3A(1), RAB6A(1)	705580	4	4	4	1	0	1	0	2	1	0.81	0.021	1

+ Methods & Data

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