Lung Squamous Cell Carcinoma: 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: LUSC.

Number of patients in set: 178

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): 386

Mutations seen in COSMIC: 1

Significantly mutated genes in COSMIC territory: 0

Genes with clustered mutations (&le 3 aa apart): 0

Significantly mutated genesets: 96

Significantly mutated genesets: (excluding sig. mutated genes): 2

Results
Breakdown of Mutations by Type

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

type count
Frame_Shift_Del 527
Frame_Shift_Ins 134
In_Frame_Del 85
In_Frame_Ins 19
Missense_Mutation 30008
Nonsense_Mutation 2526
Nonstop_Mutation 41
Silent 10780
Splice_Site 831
Translation_Start_Site 16
Total 44967
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
A->T 7968 2640254776 3e-06 3 0.48
C->(A/T) 11738 2777075010 4.2e-06 4.2 0.67
A->(C/G) 7558 2640254776 2.9e-06 2.9 0.45
C->G 2741 2777075010 9.9e-07 0.99 0.16
indel+null 4147 5417329964 7.7e-07 0.77 0.12
double_null 35 5417329964 6.5e-09 0.0065 0.001
Total 34187 5417329964 6.3e-06 6.3 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: 386. Number of genes displayed: 35

rank gene description N n npat nsite nsil n1 n2 n3 n4 n5 n6 p q
1 TP53 tumor protein p53 228196 115 113 81 4 20 20 20 13 42 0 <1.00e-15 <1.80e-11
2 CSMD3 CUB and Sushi multiple domains 3 2041660 77 59 77 16 22 22 12 5 14 2 4.44e-15 4.00e-11
3 LRP1B low density lipoprotein-related protein 1B (deleted in tumors) 2521192 69 52 67 13 20 18 19 5 7 0 7.55e-15 4.54e-11
4 HCN1 hyperpolarization activated cyclic nucleotide-gated potassium channel 1 441618 23 22 21 10 4 10 2 3 4 0 3.60e-14 9.27e-11
5 FAM5C family with sequence similarity 5, member C 414562 23 22 23 3 6 12 4 1 0 0 3.73e-14 9.27e-11
6 CDH10 cadherin 10, type 2 (T2-cadherin) 429158 27 25 27 6 8 10 3 2 4 0 4.30e-14 9.27e-11
7 CDKN2A cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4) 83838 22 22 19 1 1 5 5 0 11 0 4.41e-14 9.27e-11
8 NFE2L2 nuclear factor (erythroid-derived 2)-like 2 318442 21 20 12 0 6 0 13 1 1 0 4.76e-14 9.27e-11
9 RYR2 ryanodine receptor 2 (cardiac) 2630306 84 53 82 18 25 30 18 4 7 0 4.85e-14 9.27e-11
10 ZFHX4 zinc finger homeobox 4 1745824 64 47 64 15 21 25 9 5 4 0 5.14e-14 9.27e-11
11 USH2A Usher syndrome 2A (autosomal recessive, mild) 2831446 63 51 63 9 15 25 13 5 5 0 2.75e-13 4.50e-10
12 SI sucrase-isomaltase (alpha-glucosidase) 1009616 31 28 31 1 8 12 7 2 2 0 6.63e-12 9.96e-09
13 KEAP1 kelch-like ECH-associated protein 1 337310 17 17 16 0 3 9 2 1 2 0 9.79e-12 1.36e-08
14 ZNF804B zinc finger protein 804B 723748 24 23 23 6 7 2 8 4 3 0 1.21e-11 1.56e-08
15 TTN titin 19694276 249 120 247 79 63 76 72 16 16 6 2.49e-11 2.99e-08
16 FAM135B family with sequence similarity 135, member B 764866 31 25 31 8 8 15 6 0 2 0 2.72e-11 3.06e-08
17 CNTNAP5 contactin associated protein-like 5 680316 24 22 24 6 5 8 6 2 3 0 1.16e-10 1.23e-07
18 C1orf173 chromosome 1 open reading frame 173 819156 27 24 27 8 8 9 6 2 2 0 1.97e-10 1.97e-07
19 PTEN phosphatase and tensin homolog (mutated in multiple advanced cancers 1) 222144 13 12 13 0 2 1 3 1 6 0 2.64e-10 2.51e-07
20 ADAMTS12 ADAM metallopeptidase with thrombospondin type 1 motif, 12 868818 27 25 26 5 7 11 5 1 3 0 2.92e-10 2.63e-07
21 REG1A regenerating islet-derived 1 alpha (pancreatic stone protein, pancreatic thread protein) 92738 11 10 11 2 0 6 3 1 1 0 3.21e-10 2.76e-07
22 NAV3 neuron navigator 3 1290144 32 29 32 10 6 15 6 2 3 0 4.29e-10 3.51e-07
23 SPTA1 spectrin, alpha, erythrocytic 1 (elliptocytosis 2) 1329304 35 29 35 12 4 17 6 4 4 0 5.17e-10 3.97e-07
24 LRRC4C leucine rich repeat containing 4C 343006 18 17 18 0 11 3 3 0 1 0 5.29e-10 3.97e-07
25 ZIC1 Zic family member 1 (odd-paired homolog, Drosophila) 241368 16 13 16 4 5 4 6 0 1 0 6.90e-10 4.98e-07
26 ELTD1 EGF, latrophilin and seven transmembrane domain containing 1 375046 16 16 16 1 4 4 1 2 5 0 7.51e-10 5.21e-07
27 CDH12 cadherin 12, type 2 (N-cadherin 2) 432362 18 17 18 5 3 7 5 0 3 0 9.60e-10 6.41e-07
28 OR4M2 olfactory receptor, family 4, subfamily M, member 2 168388 11 11 11 1 3 3 2 2 1 0 1.77e-09 1.14e-06
29 COL11A1 collagen, type XI, alpha 1 1040588 31 25 31 7 7 10 8 0 6 0 2.51e-09 1.56e-06
30 DPPA4 developmental pluripotency associated 4 167854 10 10 10 0 3 2 0 1 4 0 6.93e-09 4.17e-06
31 KLHL1 kelch-like 1 (Drosophila) 407798 14 14 14 5 2 6 2 1 3 0 2.42e-08 0.000014
32 PIK3CA phosphoinositide-3-kinase, catalytic, alpha polypeptide 585086 20 19 9 1 13 3 4 0 0 0 2.49e-08 0.000014
33 PCDH11X protocadherin 11 X-linked 731758 23 20 22 3 9 8 4 2 0 0 2.52e-08 0.000014
34 OR4C6 olfactory receptor, family 4, subfamily C, member 6 166252 10 10 10 4 1 4 3 1 1 0 2.80e-08 0.000015
35 OR5D18 olfactory receptor, family 5, subfamily D, member 18 168388 10 10 10 4 4 3 2 0 1 0 3.11e-08 0.000016

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: A->T .

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

n3 - number of nonsilent mutations of type: A->(C/G) .

n4 - number of nonsilent mutations of type: C->G .

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: 0. Number of genes displayed: 10

rank gene description n cos n_cos N_cos cos_ev p q
1 SYNE1 spectrin repeat containing, nuclear envelope 1 45 22 1 3916 3 0.024 1
2 A4GNT alpha-1,4-N-acetylglucosaminyltransferase 5 0 0 0 0 1 1
3 AACS acetoacetyl-CoA synthetase 1 0 0 0 0 1 1
4 ABCA9 ATP-binding cassette, sub-family A (ABC1), member 9 9 0 0 0 0 1 1
5 ABCC10 ATP-binding cassette, sub-family C (CFTR/MRP), member 10 5 0 0 0 0 1 1
6 ABCF2 ATP-binding cassette, sub-family F (GCN20), member 2 6 0 0 0 0 1 1
7 ABHD2 abhydrolase domain containing 2 0 0 0 0 0 1 1
8 ABHD4 abhydrolase domain containing 4 1 0 0 0 0 1 1
9 ACADS acyl-Coenzyme A dehydrogenase, C-2 to C-3 short chain 2 0 0 0 0 1 1
10 ACOT11 acyl-CoA thioesterase 11 1 0 0 0 0 1 1

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 mindist npairs3 npairs12
2498 CUBN cubilin (intrinsic factor-cobalamin receptor) 21 4 0 1
27 ABCA13 ATP-binding cassette, sub-family A (ABC1), member 13 25 8 0 1
2545 CYP11B2 cytochrome P450, family 11, subfamily B, polypeptide 2 6 10 0 1
6367 MUC2 mucin 2, oligomeric mucus/gel-forming 9 11 0 1
4211 GPR98 G protein-coupled receptor 98 28 12 0 0
11134 WNK1 WNK lysine deficient protein kinase 1 14 23 0 0
9902 SYNE1 spectrin repeat containing, nuclear envelope 1 45 34 0 0
10528 TRANK1 6 47 0 0
6372 MUC6 mucin 6, oligomeric mucus/gel-forming 11 59 0 0
2296 COL7A1 collagen, type VII, alpha 1 (epidermolysis bullosa, dystrophic, dominant and recessive) 12 76 0 0

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: 96. 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 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(6), ATR(12), CDC25C(1), CHEK1(4), CHEK2(3), TP53(115) 4293716 141 122 107 5 26 27 24 18 46 0 <1.00e-15 <2.08e-13
2 ATMPATHWAY The tumor-suppressing protein kinase ATM responds to radiation-induced DNA damage by blocking cell-cycle progression and activating DNA repair. ABL1, ATM, BRCA1, CDKN1A, CHEK1, CHEK2, GADD45A, JUN, MAPK8, MDM2, MRE11A, NBS1, NFKB1, NFKBIA, RAD50, RAD51, RBBP8, RELA, TP53, TP73 19 ABL1(2), ATM(6), BRCA1(6), CHEK1(4), CHEK2(3), GADD45A(1), JUN(3), MAPK8(2), MDM2(1), NFKB1(2), RAD50(2), RAD51(1), RBBP8(1), RELA(2), TP53(115) 8101670 151 117 116 10 26 33 23 21 48 0 2.55e-15 2.08e-13
3 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(2), ATM(6), ATR(12), CDKN2A(22), E2F1(2), HDAC1(2), RB1(7), SKP2(1), TGFB1(1), TGFB2(2), TP53(115) 8079954 172 131 135 12 29 36 30 16 61 0 2.89e-15 2.08e-13
4 ST_JNK_MAPK_PATHWAY JNKs are MAP kinases regulated by several levels of kinases (MAPKK, MAPKKK) and phosphorylate transcription factors and regulatory proteins. AKT1, ATF2, CDC42, DLD, DUSP10, DUSP4, DUSP8, GAB1, GADD45A, GCK, IL1R1, JUN, MAP2K4, MAP2K5, MAP2K7, MAP3K1, MAP3K10, MAP3K11, MAP3K12, MAP3K13, MAP3K2, MAP3K3, MAP3K4, MAP3K5, MAP3K7, MAP3K7IP1, MAP3K7IP2, MAP3K9, MAPK10, MAPK7, MAPK8, MAPK9, MYEF2, NFATC3, NR2C2, PAPPA, SHC1, TP53, TRAF6, ZAK 38 AKT1(1), ATF2(2), CDC42(1), DLD(2), DUSP10(3), DUSP4(2), GAB1(2), GADD45A(1), GCK(1), JUN(3), MAP2K5(1), MAP3K1(2), MAP3K11(2), MAP3K12(3), MAP3K13(5), MAP3K4(4), MAP3K5(3), MAP3K7(2), MAP3K9(3), MAPK10(1), MAPK7(1), MAPK8(2), MAPK9(1), MYEF2(3), NFATC3(2), NR2C2(1), PAPPA(8), SHC1(1), TP53(115), TRAF6(1) 13764918 179 131 144 25 35 44 34 20 46 0 3.11e-15 2.08e-13
5 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 110 ABL1(2), ANAPC1(4), ANAPC4(3), ANAPC5(4), ATM(6), ATR(12), BUB1(3), BUB1B(6), BUB3(2), CCNB1(1), CCNB3(9), CCND2(3), CCND3(1), CCNE2(2), CDC25B(1), CDC25C(1), CDC27(2), CDC6(4), CDC7(1), CDK7(1), CDKN2A(22), CDKN2C(1), CHEK1(4), CHEK2(3), CREBBP(12), CUL1(2), DBF4(4), E2F1(2), EP300(6), ESPL1(2), GADD45A(1), GADD45G(1), HDAC1(2), MAD1L1(5), MAD2L1(2), MCM2(1), MCM3(1), MCM4(3), MCM5(6), MCM6(1), MCM7(3), MDM2(1), ORC1L(1), ORC2L(1), ORC3L(1), ORC5L(1), PKMYT1(1), PLK1(1), PRKDC(11), PTTG1(1), PTTG2(2), RB1(7), RBL1(5), RBL2(5), RBX1(1), SFN(2), SKP1(1), SKP2(1), SMAD2(1), SMAD4(2), SMC1A(2), SMC1B(4), TGFB1(1), TGFB2(2), TP53(115), WEE1(2), YWHAB(1), YWHAQ(1) 37187582 326 157 288 50 66 90 62 31 77 0 3.66e-15 2.08e-13
6 APOPTOSIS_GENMAPP APAF1, BAK1, BCL2L7P1, BAX, BCL2, BCL2L1, BID, BIRC2, BIRC3, BIRC4, CASP2, CASP3, CASP6, CASP7, CASP8, CASP9, CYCS, FADD, FAS, FASLG, GZMB, IKBKG, JUN, MAP2K4, MAP3K1, MAP3K14, MAPK10, MCL1, MDM2, MYC, NFKB1, NFKBIA, PARP1, PRF1, RELA, RIPK1, TNF, TNFRSF1A, TNFRSF1B, TNFSF10, TP53, TRADD, TRAF1, TRAF2 41 APAF1(1), BAK1(1), BAX(1), BCL2L1(1), BIRC3(3), CASP2(1), CASP7(2), CASP8(1), CASP9(2), FADD(1), FAS(1), FASLG(1), GZMB(1), JUN(3), MAP3K1(2), MAP3K14(1), MAPK10(1), MCL1(2), MDM2(1), MYC(1), NFKB1(2), PARP1(3), PRF1(1), RELA(2), TNFRSF1A(2), TNFRSF1B(1), TP53(115), TRADD(1), TRAF1(4) 10250308 159 121 124 24 30 32 26 21 50 0 4.00e-15 2.08e-13
7 ATRBRCAPATHWAY BRCA1 and 2 block cell cycle progression in response to DNA damage and promote double-stranded break repair; mutations induce breast cancer susceptibility. ATM, ATR, BRCA1, BRCA2, CHEK1, CHEK2, FANCA, FANCC, FANCD2, FANCE, FANCF, FANCG, HUS1, MRE11A, NBS1, RAD1, RAD17, RAD50, RAD51, RAD9A, TP53, TREX1 21 ATM(6), ATR(12), BRCA1(6), BRCA2(7), CHEK1(4), CHEK2(3), FANCC(2), FANCF(3), FANCG(1), RAD1(1), RAD17(2), RAD50(2), RAD51(1), RAD9A(1), TP53(115), TREX1(1) 11853198 167 124 133 14 31 36 29 21 50 0 4.77e-15 2.08e-13
8 CELL_CYCLE_KEGG ABL1, ASK, ATM, BUB1, BUB1B, BUB3, CCNA1, CCNA2, CCNB1, CCNB2, CCNB3, CCND2, CCND3, CCNE1, CCNE2, CCNH, CDAN1, CDC14A, CDC14B, CDC14B, CDC14C, CDC2, CDC20, CDC25A, CDC25B, CDC25C, CDC45L, CDC6, CDC7, CDH1, CDK2, CDK4, CDKN1A, CDKN2A, CHEK1, CHEK2, DTX4, E2F1, E2F2, E2F3, E2F4, E2F5, E2F6, EP300, ESPL1, FLJ14001, GADD45A, GSK3B, HDAC1, HDAC2, HDAC3, HDAC4, HDAC5, HDAC6, HDAC7A, HDAC8, MAD1L1, MAD2L1, MAD2L2, MCM2, MCM3, MCM4, MCM5, MCM6, MCM7, MDM2, MPEG1, MPL, ORC1L, ORC2L, ORC3L, ORC4L, ORC5L, ORC6L, PCNA, PLK1, PRKDC, PTPRA, PTTG1, PTTG2, PTTG3, RB1, RBL1, SKP2, SMAD4, SMC1L1, TBC1D8, TFDP1, TGFB1, TP53, WEE1 82 ABL1(2), ATM(6), BUB1(3), BUB1B(6), BUB3(2), CCNB1(1), CCNB3(9), CCND2(3), CCND3(1), CCNE2(2), CDAN1(3), CDC25B(1), CDC25C(1), CDC6(4), CDC7(1), CDH1(3), CDKN2A(22), CHEK1(4), CHEK2(3), DTX4(1), E2F1(2), EP300(6), ESPL1(2), GADD45A(1), HDAC1(2), HDAC3(1), HDAC4(4), HDAC5(1), MAD1L1(5), MAD2L1(2), MCM2(1), MCM3(1), MCM4(3), MCM5(6), MCM6(1), MCM7(3), MDM2(1), MPEG1(4), MPL(2), ORC1L(1), ORC2L(1), ORC3L(1), ORC5L(1), PLK1(1), PRKDC(11), PTTG1(1), PTTG2(2), RB1(7), RBL1(5), SKP2(1), SMAD4(2), TBC1D8(1), TGFB1(1), TP53(115), WEE1(2) 30149462 279 152 241 42 51 76 54 24 74 0 4.88e-15 2.08e-13
9 HSA04210_APOPTOSIS Genes involved in apoptosis AIFM1, AKT1, AKT2, AKT3, APAF1, ATM, BAD, BAX, BCL2, BCL2L1, BID, BIRC2, BIRC3, BIRC4, CAPN1, CAPN2, CASP10, CASP3, CASP6, CASP7, CASP8, CASP9, CFLAR, CHP, CHUK, CSF2RB, CYCS, DFFA, DFFB, ENDOG, FADD, FAS, FASLG, IKBKB, IKBKG, IL1A, IL1B, IL1R1, IL1RAP, IL3, IL3RA, IRAK1, IRAK2, IRAK3, IRAK4, MAP3K14, MYD88, NFKB1, NFKB2, NFKBIA, NGFB, NTRK1, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, PPP3CA, PPP3CB, PPP3CC, PPP3R1, PPP3R2, PRKACA, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, RELA, RIPK1, TNF, TNFRSF10A, TNFRSF10B, TNFRSF10C, TNFRSF10D, TNFRSF1A, TNFSF10, TP53, TRADD, TRAF2 80 AIFM1(1), AKT1(1), AKT3(2), APAF1(1), ATM(6), BAX(1), BCL2L1(1), BIRC3(3), CAPN1(2), CAPN2(2), CASP10(3), CASP7(2), CASP8(1), CASP9(2), CFLAR(1), CHP(2), CHUK(2), CSF2RB(5), DFFB(2), FADD(1), FAS(1), FASLG(1), IKBKB(2), IL1B(1), IL1RAP(2), IRAK1(3), IRAK3(3), MAP3K14(1), NFKB1(2), NFKB2(2), NTRK1(3), PIK3CA(20), PIK3CB(2), PIK3CD(3), PIK3CG(9), PIK3R1(1), PIK3R2(3), PIK3R3(2), PIK3R5(2), PPP3CA(2), PPP3CB(4), PPP3CC(2), PPP3R1(1), PPP3R2(3), PRKACB(2), PRKACG(1), PRKAR1A(2), PRKAR1B(1), PRKAR2B(2), RELA(2), TNFRSF10A(1), TNFRSF10B(1), TNFRSF1A(2), TP53(115), TRADD(1) 22576808 246 143 201 44 65 57 34 30 60 0 4.88e-15 2.08e-13
10 G2PATHWAY Activated Cdc2-cyclin B kinase regulates the G2/M transition; DNA damage stimulates the DNA-PK/ATM/ATR kinases, which inactivate Cdc2. ATM, ATR, BRCA1, CCNB1, CDC2, CDC25A, CDC25B, CDC25C, CDC34, CDKN1A, CDKN2D, CHEK1, CHEK2, EP300, GADD45A, MDM2, MYT1, PLK, PRKDC, RPS6KA1, TP53, WEE1, YWHAH, YWHAQ 22 ATM(6), ATR(12), BRCA1(6), CCNB1(1), CDC25B(1), CDC25C(1), CHEK1(4), CHEK2(3), EP300(6), GADD45A(1), MDM2(1), PRKDC(11), RPS6KA1(2), TP53(115), WEE1(2), YWHAQ(1) 11595276 173 129 138 11 32 38 32 22 49 0 5.00e-15 2.08e-13

Table 7.  Get Full Table A Ranked List of Significantly Mutated Genesets (Excluding Significantly Mutated Genes). Number of significant genesets found: 2. 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 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 225 ADORA1(3), ADORA2A(5), ADRA1A(2), ADRA1B(3), ADRA2B(4), ADRA2C(2), ADRB2(3), AGTR1(2), AGTR2(3), AVPR1A(3), AVPR1B(2), AVPR2(1), BDKRB1(1), BDKRB2(2), C3AR1(1), C5AR1(1), CALCR(5), CALCRL(3), CCKAR(2), CCKBR(1), CHRM2(6), CHRM3(4), CHRM4(1), CHRM5(2), CNR1(2), CNR2(2), CRHR1(2), CRHR2(2), CTSG(3), CYSLTR1(2), CYSLTR2(1), DRD1(1), DRD2(2), DRD3(5), DRD4(1), DRD5(3), EDNRA(1), EDNRB(3), F2R(2), F2RL1(3), F2RL2(1), F2RL3(1), FPR1(1), FSHB(1), GABBR1(1), GABBR2(2), GABRA1(6), GABRA3(4), GABRA4(3), GABRA5(4), GABRB1(3), GABRB2(5), GABRD(2), GABRE(4), GABRG2(4), GABRP(1), GABRQ(5), GABRR1(2), GABRR2(2), GALR1(3), GH2(2), GHR(2), GHRHR(3), GHSR(2), GLP1R(1), GLP2R(3), GLRA1(2), GLRA2(4), GLRA3(3), GLRB(3), GPR156(1), GPR35(1), GPR50(4), GPR63(2), GPR83(2), GRIA1(6), GRIA2(3), GRIA3(8), GRIA4(7), GRID1(10), GRID2(12), GRIK1(4), GRIK2(8), GRIK3(7), GRIK4(3), GRIK5(1), GRIN1(1), GRIN2A(13), GRIN2C(2), GRIN2D(2), GRIN3A(7), GRIN3B(4), GRM1(10), GRM2(2), GRM4(1), GRM6(4), GRM7(8), GRM8(8), GRPR(2), GZMA(4), HCRTR2(3), HRH1(3), HRH2(1), HRH3(1), HRH4(3), HTR1A(5), HTR1B(3), HTR1E(4), HTR1F(2), HTR2A(1), HTR2B(1), HTR2C(2), HTR4(3), HTR5A(3), HTR6(1), HTR7(3), LEPR(10), LHB(1), LHCGR(7), LTB4R2(1), MAS1(3), MC2R(2), MC3R(2), MC4R(1), MC5R(3), MCHR1(2), MCHR2(3), MTNR1A(1), NMBR(2), NMUR2(1), NPBWR1(1), NPY1R(3), NPY2R(2), NPY5R(2), NTSR1(3), NTSR2(2), OPRD1(1), OPRM1(2), OXTR(1), P2RX2(1), P2RX3(4), P2RX4(1), P2RX7(1), P2RY1(2), P2RY10(2), P2RY13(1), P2RY14(3), P2RY2(1), P2RY4(1), P2RY6(1), PARD3(5), PPYR1(3), PRL(1), PRLHR(1), PRLR(5), PRSS1(3), PRSS3(2), PTAFR(3), PTGDR(5), PTGER2(2), PTGER3(5), PTGER4(2), PTGFR(2), PTGIR(1), PTH2R(3), RXFP1(7), SSTR1(1), SSTR2(2), SSTR3(1), SSTR4(2), SSTR5(1), TAAR1(4), TAAR2(2), TAAR5(5), TAAR6(4), TAAR8(2), TAAR9(2), TACR1(2), TACR3(3), TBXA2R(2), THRA(1), THRB(1), TRHR(1), TRPV1(2), TSHR(1) 56455370 526 161 525 172 145 179 113 31 58 0 1.9e-09 1.2e-06
2 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 160 ADORA1(3), ADORA2A(5), ADRA1A(2), ADRA1B(3), ADRA1D(2), ADRA2C(2), ADRB2(3), AGTR1(2), AGTR2(3), AVPR1A(3), AVPR1B(2), AVPR2(1), BDKRB1(1), BDKRB2(2), C3AR1(1), CCBP2(3), CCKAR(2), CCKBR(1), CCR1(2), CCR10(1), CCR3(1), CCR4(3), CCR6(2), CCR8(1), CCRL1(2), CCRL2(1), CHML(1), CHRM2(6), CHRM3(4), CHRM4(1), CHRM5(2), CNR1(2), CNR2(2), CX3CR1(3), CXCR3(1), CXCR4(5), DRD1(1), DRD2(2), DRD3(5), DRD4(1), DRD5(3), EDNRA(1), EDNRB(3), F2R(2), F2RL1(3), F2RL2(1), F2RL3(1), FPR1(1), GALR1(3), GALT(1), GHSR(2), GPR17(3), GPR174(4), GPR27(1), GPR35(1), GPR37(2), GPR37L1(2), GPR50(4), GPR6(2), GPR63(2), GPR77(3), GPR83(2), GPR85(2), GPR87(4), GRPR(2), HCRTR2(3), HRH1(3), HRH2(1), HRH3(1), HTR1A(5), HTR1B(3), HTR1E(4), HTR1F(2), HTR2A(1), HTR2B(1), HTR2C(2), HTR4(3), HTR5A(3), HTR6(1), HTR7(3), LHCGR(7), MAS1(3), MC3R(2), MC4R(1), MC5R(3), MTNR1A(1), NMBR(2), NMUR2(1), NPY1R(3), NPY2R(2), NPY5R(2), NTSR1(3), NTSR2(2), OPN1SW(1), OPN3(1), OPRD1(1), OPRM1(2), OR10A5(1), OR11A1(3), OR12D3(4), OR1F1(1), OR1Q1(2), OR2H1(1), OR5V1(1), OXTR(1), P2RY1(2), P2RY10(2), P2RY13(1), P2RY14(3), P2RY2(1), P2RY6(1), PPYR1(3), PTAFR(3), PTGDR(5), PTGER2(2), PTGER4(2), PTGFR(2), PTGIR(1), RGR(1), RHO(1), SSTR1(1), SSTR2(2), SSTR3(1), SSTR4(2), SUCNR1(2), TBXA2R(2), TRHR(1) 32196462 273 134 273 97 70 95 61 15 32 0 0.000019 0.0058
3 HSA04614_RENIN_ANGIOTENSIN_SYSTEM Genes involved in renin-angiotensin system ACE, ACE2, AGT, AGTR1, AGTR2, ANPEP, CMA1, CPA3, CTSA, CTSG, ENPEP, LNPEP, MAS1, MME, NLN, REN, THOP1 17 ACE(4), ACE2(3), AGT(1), AGTR1(2), AGTR2(3), ANPEP(5), CMA1(2), CPA3(4), CTSA(2), CTSG(3), ENPEP(7), LNPEP(2), MAS1(3), MME(8), NLN(2), THOP1(1) 5741924 52 46 52 14 10 21 8 4 9 0 0.0012 0.24
4 MONOAMINE_GPCRS ADRA1A, ADRA1B, ADRA1D, ADRA2A, ADRA2C, ADRB1, ADRB2, ADRB3, CHRM1, CHRM2, CHRM3, CHRM4, CHRM5, DRD1, DRD2, DRD3, DRD4, DRD5, HRH1, HRH2, HTR1A, HTR1B, HTR1D, HTR1E, HTR1F, HTR2A, HTR2B, HTR2C, HTR4, HTR5A, HTR6, HTR7, HTR7, LOC93164 32 ADRA1A(2), ADRA1B(3), ADRA1D(2), ADRA2C(2), ADRB2(3), CHRM2(6), CHRM3(4), CHRM4(1), CHRM5(2), DRD1(1), DRD2(2), DRD3(5), DRD4(1), DRD5(3), HRH1(3), HRH2(1), HTR1A(5), HTR1B(3), HTR1E(4), HTR1F(2), HTR2A(1), HTR2B(1), HTR2C(2), HTR4(3), HTR5A(3), HTR6(1), HTR7(3) 7002876 69 51 69 27 15 25 22 3 4 0 0.0026 0.39
5 FLUMAZENILPATHWAY Flumazenil is a benzodiazepine receptor antagonist that may induce protective preconditioning in ischemic cardiomyocytes. GABRA1, GABRA2, GABRA3, GABRA4, GABRA5, GABRA6, GPX1, PRKCE, SOD1 7 GABRA1(6), GABRA3(4), GABRA4(3), GABRA5(4), PRKCE(3) 1635108 20 19 20 4 8 7 3 0 2 0 0.0046 0.39
6 HSA01430_CELL_COMMUNICATION Genes involved in cell communication ACTB, ACTG1, CHAD, COL11A1, COL11A2, COL17A1, COL1A1, COL1A2, COL2A1, COL3A1, COL4A1, COL4A2, COL4A4, COL4A6, COL5A1, COL5A2, COL5A3, COL6A1, COL6A2, COL6A3, COL6A6, COMP, DES, DSC1, DSC2, DSC3, DSG1, DSG2, DSG3, DSG4, FN1, GJA1, GJA10, GJA3, GJA4, GJA5, GJA8, GJA9, GJB1, GJB2, GJB3, GJB4, GJB5, GJB6, GJB7, GJC1, GJC2, GJC3, GJD2, GJD3, GJD4, IBSP, INA, ITGA6, ITGB4, KRT1, KRT10, KRT12, KRT13, KRT14, KRT15, KRT16, KRT17, KRT18, KRT19, KRT2, KRT20, KRT23, KRT24, KRT25, KRT27, KRT28, KRT3, KRT31, KRT32, KRT33A, KRT33B, KRT34, KRT35, KRT36, KRT37, KRT38, KRT39, KRT4, KRT40, KRT5, KRT6A, KRT6B, KRT6C, KRT7, KRT71, KRT72, KRT73, KRT74, KRT75, KRT76, KRT77, KRT78, KRT79, KRT8, KRT81, KRT82, KRT83, KRT84, KRT85, KRT86, KRT9, LAMA1, LAMA2, LAMA3, LAMA4, LAMA5, LAMB1, LAMB2, LAMB3, LAMB4, LAMC1, LAMC2, LAMC3, LMNA, LMNB1, LMNB2, LOC728760, NES, PRPH, RELN, SPP1, THBS1, THBS2, THBS3, THBS4, TNC, TNN, TNR, TNXB, VIM, VTN, VWF 130 ACTB(1), COL11A2(10), COL17A1(4), COL1A1(8), COL1A2(12), COL2A1(8), COL3A1(10), COL4A1(6), COL4A2(6), COL4A4(9), COL4A6(6), COL5A1(5), COL5A2(11), COL5A3(11), COL6A3(10), COMP(1), DES(2), DSC1(5), DSC2(1), DSC3(6), DSG1(8), DSG2(2), DSG3(3), DSG4(5), FN1(16), GJA1(4), GJA10(5), GJA8(3), GJA9(1), GJB2(1), GJB4(1), GJC1(2), GJC2(1), GJC3(1), GJD2(2), GJD4(2), IBSP(4), INA(2), ITGA6(3), ITGB4(6), KRT1(1), KRT10(1), KRT12(3), KRT13(2), KRT14(1), KRT16(3), KRT17(2), KRT18(2), KRT2(4), KRT20(2), KRT23(2), KRT24(3), KRT27(2), KRT28(1), KRT3(2), KRT31(1), KRT32(2), KRT33A(1), KRT35(1), KRT36(2), KRT37(2), KRT4(1), KRT5(1), KRT6A(1), KRT6B(2), KRT71(2), KRT72(2), KRT73(6), KRT75(1), KRT76(2), KRT77(3), KRT79(3), KRT81(3), KRT82(1), KRT84(1), KRT85(1), KRT9(1), LAMA1(12), LAMA2(18), LAMA3(7), LAMA4(13), LAMA5(6), LAMB1(5), LAMB2(2), LAMB3(1), LAMB4(3), LAMC1(8), LAMC2(2), LAMC3(1), NES(11), PRPH(2), RELN(24), THBS1(1), THBS3(3), THBS4(1), TNC(11), TNXB(15), VIM(4), VWF(15) 63492600 440 149 440 126 114 153 95 32 46 0 0.0046 0.39
7 GPCRDB_CLASS_C_METABOTROPIC_GLUTAMATE_PHEROMONE CASR, GABBR1, GPCR5A, GPR51, GPRC5A, GPRC5B, GPRC5C, GPRC5D, GRM1, GRM2, GRM3, GRM4, GRM5, GRM7, GRM8 11 CASR(8), GABBR1(1), GPRC5A(1), GPRC5C(4), GRM1(10), GRM2(2), GRM4(1), GRM7(8), GRM8(8) 4577092 43 36 43 18 8 12 11 6 6 0 0.0049 0.39
8 BLOOD_CLOTTING_CASCADE F10, F11, F12, F13B, F2, F5, F7, F8, F8A1, F9, FGA, FGB, FGG, LPA, PLG, PLAT, PLAU, PLG, SERPINB2, SERPINE1, SERPINF2, VWF 19 F10(3), F11(3), F12(1), F5(14), F8(9), F9(4), FGA(5), FGB(3), FGG(1), LPA(11), PLAT(1), PLAU(2), PLG(1), SERPINB2(3), SERPINF2(3), VWF(15) 9118406 79 59 79 17 12 31 22 6 8 0 0.0054 0.39
9 HSA04720_LONG_TERM_POTENTIATION Genes involved in long-term potentiation ADCY1, ADCY8, ARAF, ATF4, BRAF, CACNA1C, CALM1, CALM2, CALM3, CALML3, CALML6, CAMK2A, CAMK2B, CAMK2D, CAMK2G, CAMK4, CHP, CREBBP, EP300, GNAQ, GRIA1, GRIA2, GRIN1, GRIN2A, GRIN2B, GRIN2C, GRIN2D, GRM1, GRM5, HRAS, ITPR1, ITPR2, ITPR3, KRAS, MAP2K1, MAP2K2, MAPK1, MAPK3, NRAS, PLCB1, PLCB2, PLCB3, PLCB4, PPP1CA, PPP1CB, PPP1CC, PPP1R12A, PPP1R1A, PPP3CA, PPP3CB, PPP3CC, PPP3R1, PPP3R2, PRKACA, PRKACB, PRKACG, PRKCA, PRKCB1, PRKCG, PRKX, PRKY, RAF1, RAP1A, RAP1B, RAPGEF3, RPS6KA1, RPS6KA2, RPS6KA3, RPS6KA6 65 ADCY1(7), ADCY8(13), ARAF(3), BRAF(7), CACNA1C(12), CALML6(1), CAMK2B(2), CAMK2D(1), CAMK4(3), CHP(2), CREBBP(12), EP300(6), GRIA1(6), GRIA2(3), GRIN1(1), GRIN2A(13), GRIN2C(2), GRIN2D(2), GRM1(10), HRAS(1), ITPR1(4), ITPR2(11), ITPR3(1), KRAS(1), MAP2K1(2), MAPK1(1), MAPK3(1), PLCB1(6), PLCB2(5), PLCB3(3), PLCB4(4), PPP3CA(2), PPP3CB(4), PPP3CC(2), PPP3R1(1), PPP3R2(3), PRKACB(2), PRKACG(1), PRKCA(4), PRKCG(8), PRKX(1), RAF1(1), RAP1B(1), RPS6KA1(2), RPS6KA2(3), RPS6KA3(1), RPS6KA6(4) 26244498 186 110 185 56 56 53 34 22 21 0 0.0058 0.39
10 C21_STEROID_HORMONE_METABOLISM AKR1C4, AKR1D1, CYP11A1, CYP11B1, CYP11B2, CYP17A1, CYP21A2, HSD11B1, HSD11B2, HSD3B1, HSD3B2 9 AKR1C4(1), AKR1D1(4), CYP11A1(2), CYP17A1(1), CYP21A2(2), HSD11B1(3), HSD11B2(1), HSD3B1(4), HSD3B2(3) 1875230 21 19 21 2 5 8 3 3 2 0 0.0069 0.39
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]

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References
[1] TCGA, Integrated genomic analyses of ovarian carcinoma, Nature 474:609 Ð 615 (2011)
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  • Maintainer = Dan DiCara

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