Correlation between copy number variation genes and molecular subtypes

Sarcoma (Primary solid tumor)

21 April 2013 | analyses__2013_04_21

Maintainer Information

Citation Information

Maintained by TCGA GDAC Team (Broad Institute/MD Anderson Cancer Center/Harvard Medical School)

Cite as Broad Institute TCGA Genome Data Analysis Center (2013): Sarcoma (Primary solid tumor cohort) - 21 April 2013: Correlation between copy number variation genes and molecular subtypes. Broad Institute of MIT and Harvard. doi:10.7908/C1DB7ZT7

Overview

Introduction

This pipeline computes the correlation between significant copy number variation (cnv) genes and molecular subtypes.

Summary

Testing the association between copy number variation of 40 peak regions and 4 molecular subtypes across 51 patients, 8 significant findings detected with Q value < 0.25.

Amp Peak 7(7p15.3) cnvs correlated to 'CN_CNMF'.
Amp Peak 10(12q15) cnvs correlated to 'CN_CNMF', 'METHLYATION_CNMF', 'MIRSEQ_CNMF', and 'MIRSEQ_CHIERARCHICAL'.
Del Peak 2(1p32.3) cnvs correlated to 'CN_CNMF'.
Del Peak 5(3p21.31) cnvs correlated to 'CN_CNMF'.
Del Peak 12(9p21.3) cnvs correlated to 'CN_CNMF'.

Results

Overview of the results

Table 1. Get Full Table Overview of the association between significant copy number variation of 40 regions and 4 molecular subtypes. Shown in the table are P values (Q values). Thresholded by Q value < 0.25, 8 significant findings detected.


		Molecular subtypes	CN CNMF	METHLYATION CNMF	MIRSEQ CNMF	MIRSEQ CHIERARCHICAL
	nCNV (%)	nWild-Type	Fisher's exact test	Fisher's exact test	Fisher's exact test	Fisher's exact test
Amp Peak 10(12q15)	0 (0%)	25	5.35e-05 (0.0084)	5.92e-08 (9.47e-06)	2.19e-05 (0.00348)	2.91e-05 (0.0046)
Amp Peak 7(7p15 3)	0 (0%)	32	0.000443 (0.0683)	0.0166 (1.00)	0.114 (1.00)	0.152 (1.00)
Del Peak 2(1p32 3)	0 (0%)	38	0.00103 (0.157)	0.524 (1.00)	0.0638 (1.00)	0.0295 (1.00)
Del Peak 5(3p21 31)	0 (0%)	36	0.000289 (0.0451)	0.0157 (1.00)	0.238 (1.00)	0.0569 (1.00)
Del Peak 12(9p21 3)	0 (0%)	27	0.000432 (0.0669)	0.0394 (1.00)	0.702 (1.00)	0.24 (1.00)
Amp Peak 1(1p32 1)	0 (0%)	36	0.158 (1.00)	0.221 (1.00)	0.13 (1.00)	0.278 (1.00)
Amp Peak 2(1q24 3)	0 (0%)	29	0.451 (1.00)	0.406 (1.00)	1 (1.00)	1 (1.00)
Amp Peak 3(4p15 2)	0 (0%)	35	0.231 (1.00)	0.0567 (1.00)	0.697 (1.00)	1 (1.00)
Amp Peak 4(5p14 2)	0 (0%)	30	0.628 (1.00)	0.356 (1.00)	0.697 (1.00)	1 (1.00)
Amp Peak 5(6p21 1)	0 (0%)	39	0.645 (1.00)	0.00302 (0.452)	0.41 (1.00)	0.743 (1.00)
Amp Peak 6(6q25 1)	0 (0%)	37	0.044 (1.00)	0.00284 (0.429)	0.13 (1.00)	0.278 (1.00)
Amp Peak 8(11q22 2)	0 (0%)	39	0.645 (1.00)	0.131 (1.00)	0.0205 (1.00)	0.0463 (1.00)
Amp Peak 9(12p13 32)	0 (0%)	36	0.0792 (1.00)	0.395 (1.00)	0.0927 (1.00)	0.225 (1.00)
Amp Peak 11(17p12)	0 (0%)	33	0.0209 (1.00)	0.761 (1.00)	0.192 (1.00)	0.103 (1.00)
Amp Peak 12(19p13 2)	0 (0%)	30	0.00571 (0.851)	0.771 (1.00)	0.41 (1.00)	0.0647 (1.00)
Amp Peak 13(Xq21 1)	0 (0%)	41	0.213 (1.00)	0.0807 (1.00)	1 (1.00)	1 (1.00)
Del Peak 1(1p36 32)	0 (0%)	33	0.533 (1.00)	0.0501 (1.00)	0.226 (1.00)	0.0985 (1.00)
Del Peak 3(1q44)	0 (0%)	33	0.0152 (1.00)	0.00212 (0.322)	0.697 (1.00)	1 (1.00)
Del Peak 4(2q37 3)	0 (0%)	27	0.0738 (1.00)	0.212 (1.00)	0.272 (1.00)	0.345 (1.00)
Del Peak 6(3q25 1)	0 (0%)	34	0.0198 (1.00)	0.0909 (1.00)	0.13 (1.00)	0.0388 (1.00)
Del Peak 7(4q35 1)	0 (0%)	26	0.0977 (1.00)	0.3 (1.00)	0.264 (1.00)	0.264 (1.00)
Del Peak 8(5q23 3)	0 (0%)	41	0.549 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)
Del Peak 9(6q15)	0 (0%)	37	0.62 (1.00)	0.532 (1.00)	0.663 (1.00)	0.119 (1.00)
Del Peak 10(7q36 3)	0 (0%)	37	0.376 (1.00)	0.532 (1.00)	0.663 (1.00)	0.741 (1.00)
Del Peak 11(8p23 2)	0 (0%)	35	0.0561 (1.00)	0.0661 (1.00)	0.249 (1.00)	0.0769 (1.00)
Del Peak 13(9q34 3)	0 (0%)	36	0.857 (1.00)	0.119 (1.00)	1 (1.00)	1 (1.00)
Del Peak 14(10p15 3)	0 (0%)	28	0.266 (1.00)	0.728 (1.00)	0.466 (1.00)	0.422 (1.00)
Del Peak 15(11p15 5)	0 (0%)	28	0.591 (1.00)	1 (1.00)	1 (1.00)	0.438 (1.00)
Del Peak 16(11q22 3)	0 (0%)	30	0.00672 (0.995)	0.205 (1.00)	0.716 (1.00)	0.825 (1.00)
Del Peak 17(11q24 3)	0 (0%)	28	0.0892 (1.00)	0.177 (1.00)	1 (1.00)	1 (1.00)
Del Peak 18(12p12 3)	0 (0%)	38	0.113 (1.00)	0.222 (1.00)	0.454 (1.00)	0.784 (1.00)
Del Peak 19(13q14 2)	0 (0%)	14	1 (1.00)	0.212 (1.00)	0.433 (1.00)	0.629 (1.00)
Del Peak 20(14q24 1)	0 (0%)	26	0.0303 (1.00)	0.361 (1.00)	0.272 (1.00)	0.345 (1.00)
Del Peak 21(17p13 1)	0 (0%)	36	0.0228 (1.00)	0.0437 (1.00)	0.406 (1.00)	0.443 (1.00)
Del Peak 22(17q25 3)	0 (0%)	37	0.411 (1.00)	0.681 (1.00)	1 (1.00)	1 (1.00)
Del Peak 23(19p13 3)	0 (0%)	36	0.147 (1.00)	0.0797 (1.00)	1 (1.00)	1 (1.00)
Del Peak 24(19q13 33)	0 (0%)	34	0.866 (1.00)	0.149 (1.00)	0.466 (1.00)	0.422 (1.00)
Del Peak 25(21q22 3)	0 (0%)	31	0.254 (1.00)	0.52 (1.00)	0.702 (1.00)	0.817 (1.00)
Del Peak 26(Xq21 1)	0 (0%)	25	0.489 (1.00)	0.234 (1.00)	0.462 (1.00)	0.579 (1.00)
Del Peak 27(Xq28)	0 (0%)	26	0.636 (1.00)	0.0211 (1.00)	0.274 (1.00)	0.251 (1.00)

'Amp Peak 7(7p15.3)' versus 'CN_CNMF'

P value = 0.000443 (Fisher's exact test), Q value = 0.068

Table S1. Gene #7: 'Amp Peak 7(7p15.3)' versus Molecular Subtype #1: 'CN_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	13	16	22
AMP PEAK 7(7P15.3) CNV	6	11	2
AMP PEAK 7(7P15.3) WILD-TYPE	7	5	20

Figure S1. Get High-res Image Gene #7: 'Amp Peak 7(7p15.3)' versus Molecular Subtype #1: 'CN_CNMF'

'Amp Peak 10(12q15)' versus 'CN_CNMF'

P value = 5.35e-05 (Fisher's exact test), Q value = 0.0084

Table S2. Gene #10: 'Amp Peak 10(12q15)' versus Molecular Subtype #1: 'CN_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	13	16	22
AMP PEAK 10(12Q15) CNV	13	7	6
AMP PEAK 10(12Q15) WILD-TYPE	0	9	16

Figure S2. Get High-res Image Gene #10: 'Amp Peak 10(12q15)' versus Molecular Subtype #1: 'CN_CNMF'

'Amp Peak 10(12q15)' versus 'METHLYATION_CNMF'

P value = 5.92e-08 (Fisher's exact test), Q value = 9.5e-06

Table S3. Gene #10: 'Amp Peak 10(12q15)' versus Molecular Subtype #2: 'METHLYATION_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	18	15	18
AMP PEAK 10(12Q15) CNV	14	12	0
AMP PEAK 10(12Q15) WILD-TYPE	4	3	18

Figure S3. Get High-res Image Gene #10: 'Amp Peak 10(12q15)' versus Molecular Subtype #2: 'METHLYATION_CNMF'

'Amp Peak 10(12q15)' versus 'MIRSEQ_CNMF'

P value = 2.19e-05 (Fisher's exact test), Q value = 0.0035

Table S4. Gene #10: 'Amp Peak 10(12q15)' versus Molecular Subtype #3: 'MIRSEQ_CNMF'

nPatients	CLUS_1	CLUS_2
ALL	16	13
AMP PEAK 10(12Q15) CNV	14	1
AMP PEAK 10(12Q15) WILD-TYPE	2	12

Figure S4. Get High-res Image Gene #10: 'Amp Peak 10(12q15)' versus Molecular Subtype #3: 'MIRSEQ_CNMF'

'Amp Peak 10(12q15)' versus 'MIRSEQ_CHIERARCHICAL'

P value = 2.91e-05 (Fisher's exact test), Q value = 0.0046

Table S5. Gene #10: 'Amp Peak 10(12q15)' versus Molecular Subtype #4: 'MIRSEQ_CHIERARCHICAL'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	1	12	16
AMP PEAK 10(12Q15) CNV	0	1	14
AMP PEAK 10(12Q15) WILD-TYPE	1	11	2

Figure S5. Get High-res Image Gene #10: 'Amp Peak 10(12q15)' versus Molecular Subtype #4: 'MIRSEQ_CHIERARCHICAL'

'Del Peak 2(1p32.3)' versus 'CN_CNMF'

P value = 0.00103 (Fisher's exact test), Q value = 0.16

Table S6. Gene #15: 'Del Peak 2(1p32.3)' versus Molecular Subtype #1: 'CN_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	13	16	22
DEL PEAK 2(1P32.3) CNV	0	9	4
DEL PEAK 2(1P32.3) WILD-TYPE	13	7	18

Figure S6. Get High-res Image Gene #15: 'Del Peak 2(1p32.3)' versus Molecular Subtype #1: 'CN_CNMF'

'Del Peak 5(3p21.31)' versus 'CN_CNMF'

P value = 0.000289 (Fisher's exact test), Q value = 0.045

Table S7. Gene #18: 'Del Peak 5(3p21.31)' versus Molecular Subtype #1: 'CN_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	13	16	22
DEL PEAK 5(3P21.31) CNV	4	10	1
DEL PEAK 5(3P21.31) WILD-TYPE	9	6	21

Figure S7. Get High-res Image Gene #18: 'Del Peak 5(3p21.31)' versus Molecular Subtype #1: 'CN_CNMF'

'Del Peak 12(9p21.3)' versus 'CN_CNMF'

P value = 0.000432 (Fisher's exact test), Q value = 0.067

Table S8. Gene #25: 'Del Peak 12(9p21.3)' versus Molecular Subtype #1: 'CN_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	13	16	22
DEL PEAK 12(9P21.3) CNV	7	13	4
DEL PEAK 12(9P21.3) WILD-TYPE	6	3	18

Figure S8. Get High-res Image Gene #25: 'Del Peak 12(9p21.3)' versus Molecular Subtype #1: 'CN_CNMF'

Methods & Data

Input

Copy number data file = All Lesions File (all_lesions.conf_##.txt, where ## is the confidence level). The all lesions file is from GISTIC pipeline and summarizes the results from the GISTIC run. It contains data about the significant regions of amplification and deletion as well as which samples are amplified or deleted in each of these regions. The identified regions are listed down the first column, and the samples are listed across the first row, starting in column 10.
Molecular subtype file = SARC-TP.transferedmergedcluster.txt
Number of patients = 51
Number of copy number variation regions = 40
Number of molecular subtypes = 4
Exclude regions that fewer than K tumors have alterations, K = 3

Fisher's exact test

For binary or multi-class clinical features (nominal or ordinal), two-tailed Fisher's exact tests (Fisher 1922) were used to estimate the P values using the 'fisher.test' function in R

Q value calculation

For multiple hypothesis correction, Q value is the False Discovery Rate (FDR) analogue of the P value (Benjamini and Hochberg 1995), defined as the minimum FDR at which the test may be called significant. We used the 'Benjamini and Hochberg' method of 'p.adjust' function in R to convert P values into Q values.

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] Fisher, R.A., On the interpretation of chi-square from contingency tables, and the calculation of P, Journal of the Royal Statistical Society 85(1):87-94 (1922)

[2] Benjamini and Hochberg, Controlling the false discovery rate: a practical and powerful approach to multiple testing, Journal of the Royal Statistical Society Series B 59:289-300 (1995)

[3] GISTIC_version2

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