Correlation between copy number variation genes and molecular subtypes

Liver Hepatocellular Carcinoma (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): Liver Hepatocellular Carcinoma (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/C1057CWN

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 53 peak regions and 6 molecular subtypes across 97 patients, 10 significant findings detected with Q value < 0.25.

Amp Peak 2(1q22) cnvs correlated to 'METHLYATION_CNMF'.
Amp Peak 11(6p21.1) cnvs correlated to 'METHLYATION_CNMF'.
Amp Peak 14(8q13.1) cnvs correlated to 'CN_CNMF'.
Amp Peak 15(8q24.13) cnvs correlated to 'CN_CNMF'.
Amp Peak 18(12q23.1) cnvs correlated to 'CN_CNMF'.
Amp Peak 24(17q25.3) cnvs correlated to 'CN_CNMF'.
Del Peak 4(3p13) cnvs correlated to 'MRNASEQ_CHIERARCHICAL'.
Del Peak 5(4q24) cnvs correlated to 'CN_CNMF'.
Del Peak 10(8p23.2) cnvs correlated to 'CN_CNMF'.
Del Peak 21(16q23.1) 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 53 regions and 6 molecular subtypes. Shown in the table are P values (Q values). Thresholded by Q value < 0.25, 10 significant findings detected.


		Molecular subtypes	CN CNMF	METHLYATION CNMF	MRNASEQ CNMF	MRNASEQ CHIERARCHICAL	MIRSEQ CNMF	MIRSEQ CHIERARCHICAL
	nCNV (%)	nWild-Type	Fisher's exact test	Fisher's exact test	Chi-square test	Fisher's exact test	Fisher's exact test	Fisher's exact test
Amp Peak 2(1q22)	0 (0%)	25	0.00126 (0.385)	0.000571 (0.177)	0.131 (1.00)	0.581 (1.00)	0.412 (1.00)	0.723 (1.00)
Amp Peak 11(6p21 1)	0 (0%)	54	0.00087 (0.268)	7.43e-05 (0.0234)	0.00623 (1.00)	0.332 (1.00)	0.346 (1.00)	1 (1.00)
Amp Peak 14(8q13 1)	0 (0%)	48	4.22e-09 (1.34e-06)	0.931 (1.00)	0.149 (1.00)	1 (1.00)	0.38 (1.00)	0.523 (1.00)
Amp Peak 15(8q24 13)	0 (0%)	37	1.8e-07 (5.7e-05)	0.737 (1.00)	0.178 (1.00)	0.623 (1.00)	0.4 (1.00)	0.743 (1.00)
Amp Peak 18(12q23 1)	0 (0%)	78	0.00045 (0.14)	0.0737 (1.00)	0.668 (1.00)	0.131 (1.00)	0.472 (1.00)	0.452 (1.00)
Amp Peak 24(17q25 3)	0 (0%)	53	0.000453 (0.141)	0.0959 (1.00)	0.388 (1.00)	0.811 (1.00)	0.929 (1.00)	0.533 (1.00)
Del Peak 4(3p13)	0 (0%)	81	0.113 (1.00)	0.292 (1.00)	0.00238 (0.724)	0.000163 (0.051)	0.00806 (1.00)	0.208 (1.00)
Del Peak 5(4q24)	0 (0%)	56	8.47e-05 (0.0266)	0.131 (1.00)	0.412 (1.00)	0.809 (1.00)	0.141 (1.00)	1 (1.00)
Del Peak 10(8p23 2)	0 (0%)	37	3.6e-07 (0.000114)	0.467 (1.00)	0.234 (1.00)	0.46 (1.00)	0.492 (1.00)	0.195 (1.00)
Del Peak 21(16q23 1)	0 (0%)	55	0.00075 (0.232)	0.00819 (1.00)	0.0114 (1.00)	0.0538 (1.00)	0.305 (1.00)	0.338 (1.00)
Amp Peak 1(1p22 3)	0 (0%)	73	0.0686 (1.00)	0.363 (1.00)	0.218 (1.00)	0.112 (1.00)	0.206 (1.00)	0.279 (1.00)
Amp Peak 3(1q42 3)	0 (0%)	32	0.00359 (1.00)	0.0103 (1.00)	0.0429 (1.00)	0.802 (1.00)	0.532 (1.00)	0.496 (1.00)
Amp Peak 4(2p24 1)	0 (0%)	75	0.244 (1.00)	0.387 (1.00)	0.702 (1.00)	0.25 (1.00)	0.164 (1.00)	0.705 (1.00)
Amp Peak 5(2q33 1)	0 (0%)	77	0.263 (1.00)	0.576 (1.00)	0.491 (1.00)	0.771 (1.00)	0.633 (1.00)	1 (1.00)
Amp Peak 6(3q26 31)	0 (0%)	77	0.00568 (1.00)	0.328 (1.00)	0.126 (1.00)	1 (1.00)	0.378 (1.00)	0.224 (1.00)
Amp Peak 7(4q31 3)	0 (0%)	89	0.524 (1.00)	1 (1.00)	0.465 (1.00)	0.122 (1.00)	0.0467 (1.00)	0.235 (1.00)
Amp Peak 8(5p15 33)	0 (0%)	49	0.00278 (0.842)	0.522 (1.00)	0.165 (1.00)	0.0938 (1.00)	0.3 (1.00)	0.523 (1.00)
Amp Peak 9(5q35 3)	0 (0%)	60	0.0315 (1.00)	0.416 (1.00)	0.358 (1.00)	0.443 (1.00)	1 (1.00)	1 (1.00)
Amp Peak 10(6p25 2)	0 (0%)	55	0.0102 (1.00)	0.00334 (1.00)	0.118 (1.00)	0.0938 (1.00)	0.766 (1.00)	0.754 (1.00)
Amp Peak 12(6q12)	0 (0%)	65	0.0651 (1.00)	0.0286 (1.00)	0.101 (1.00)	1 (1.00)	0.0695 (1.00)	0.322 (1.00)
Amp Peak 13(7q21 2)	0 (0%)	61	0.253 (1.00)	0.0438 (1.00)	0.397 (1.00)	0.2 (1.00)	0.665 (1.00)	0.317 (1.00)
Amp Peak 16(10p15 1)	0 (0%)	78	0.168 (1.00)	0.256 (1.00)	0.273 (1.00)	0.0167 (1.00)	0.447 (1.00)	0.689 (1.00)
Amp Peak 17(11q13 3)	0 (0%)	80	0.396 (1.00)	0.486 (1.00)	0.16 (1.00)	0.732 (1.00)	0.116 (1.00)	0.108 (1.00)
Amp Peak 19(13q32 3)	0 (0%)	75	0.0011 (0.339)	0.128 (1.00)	0.372 (1.00)	0.144 (1.00)	0.536 (1.00)	0.121 (1.00)
Amp Peak 20(15q21 3)	0 (0%)	82	0.013 (1.00)	0.365 (1.00)	0.153 (1.00)	0.542 (1.00)	0.932 (1.00)	1 (1.00)
Amp Peak 21(15q26 3)	0 (0%)	82	0.036 (1.00)	0.81 (1.00)	0.61 (1.00)	0.542 (1.00)	0.932 (1.00)	1 (1.00)
Amp Peak 22(17p11 2)	0 (0%)	82	0.00313 (0.945)	0.755 (1.00)	0.256 (1.00)	0.302 (1.00)	0.82 (1.00)	0.202 (1.00)
Amp Peak 23(17q23 1)	0 (0%)	57	0.023 (1.00)	0.513 (1.00)	0.301 (1.00)	0.22 (1.00)	0.892 (1.00)	0.754 (1.00)
Amp Peak 25(19q13 11)	0 (0%)	66	0.0411 (1.00)	0.283 (1.00)	0.686 (1.00)	0.302 (1.00)	0.462 (1.00)	0.32 (1.00)
Amp Peak 26(20q13 13)	0 (0%)	62	0.0418 (1.00)	0.556 (1.00)	0.00449 (1.00)	0.461 (1.00)	0.885 (1.00)	0.519 (1.00)
Del Peak 1(1p36 32)	0 (0%)	52	0.0159 (1.00)	0.0145 (1.00)	0.276 (1.00)	0.631 (1.00)	0.661 (1.00)	0.218 (1.00)
Del Peak 2(2q22 1)	0 (0%)	87	0.489 (1.00)	0.392 (1.00)	0.751 (1.00)	0.69 (1.00)	0.0432 (1.00)	0.0911 (1.00)
Del Peak 3(2q37 3)	0 (0%)	81	0.357 (1.00)	0.563 (1.00)	0.442 (1.00)	0.75 (1.00)	0.0724 (1.00)	0.0886 (1.00)
Del Peak 6(4q35 1)	0 (0%)	55	0.00205 (0.624)	0.0465 (1.00)	0.116 (1.00)	0.337 (1.00)	0.181 (1.00)	0.532 (1.00)
Del Peak 7(5q23 1)	0 (0%)	83	0.156 (1.00)	0.228 (1.00)	0.335 (1.00)	0.152 (1.00)	0.266 (1.00)	0.208 (1.00)
Del Peak 8(6q16 3)	0 (0%)	61	0.304 (1.00)	0.707 (1.00)	0.419 (1.00)	0.127 (1.00)	0.64 (1.00)	1 (1.00)
Del Peak 9(6q26)	0 (0%)	58	0.165 (1.00)	0.714 (1.00)	0.669 (1.00)	0.127 (1.00)	0.294 (1.00)	0.747 (1.00)
Del Peak 11(9p21 3)	0 (0%)	58	0.155 (1.00)	0.772 (1.00)	0.781 (1.00)	0.337 (1.00)	0.365 (1.00)	0.342 (1.00)
Del Peak 12(10p15 3)	0 (0%)	89	0.731 (1.00)	0.893 (1.00)	0.42 (1.00)	0.634 (1.00)	0.317 (1.00)	0.235 (1.00)
Del Peak 13(10q23 31)	0 (0%)	66	0.0337 (1.00)	0.637 (1.00)	0.00548 (1.00)	0.0722 (1.00)	0.082 (1.00)	0.169 (1.00)
Del Peak 14(10q24 33)	0 (0%)	68	0.051 (1.00)	0.577 (1.00)	0.0056 (1.00)	0.0647 (1.00)	0.0152 (1.00)	0.0881 (1.00)
Del Peak 15(11q14 1)	0 (0%)	79	0.576 (1.00)	0.751 (1.00)	0.429 (1.00)	0.554 (1.00)	0.94 (1.00)	1 (1.00)
Del Peak 16(12p12 1)	0 (0%)	74	0.184 (1.00)	0.863 (1.00)	0.248 (1.00)	0.177 (1.00)	0.12 (1.00)	0.018 (1.00)
Del Peak 17(12q24 33)	0 (0%)	81	0.484 (1.00)	1 (1.00)	0.593 (1.00)	0.75 (1.00)	0.153 (1.00)	0.391 (1.00)
Del Peak 18(13q14 2)	0 (0%)	54	0.00682 (1.00)	0.148 (1.00)	0.0528 (1.00)	0.0538 (1.00)	0.0294 (1.00)	0.532 (1.00)
Del Peak 19(14q23 3)	0 (0%)	61	0.022 (1.00)	0.292 (1.00)	0.401 (1.00)	0.0482 (1.00)	0.726 (1.00)	0.017 (1.00)
Del Peak 20(15q15 1)	0 (0%)	79	0.00375 (1.00)	0.591 (1.00)	0.364 (1.00)	0.0341 (1.00)	0.73 (1.00)	1 (1.00)
Del Peak 22(17p12)	0 (0%)	40	0.0921 (1.00)	0.515 (1.00)	0.121 (1.00)	0.139 (1.00)	0.00447 (1.00)	0.0258 (1.00)
Del Peak 23(18q21 2)	0 (0%)	79	0.118 (1.00)	0.126 (1.00)	0.132 (1.00)	1 (1.00)	0.506 (1.00)	1 (1.00)
Del Peak 24(19p13 3)	0 (0%)	77	0.0516 (1.00)	0.101 (1.00)	0.503 (1.00)	0.267 (1.00)	0.146 (1.00)	0.0521 (1.00)
Del Peak 25(22q12 1)	0 (0%)	79	0.0318 (1.00)	0.239 (1.00)	0.123 (1.00)	0.235 (1.00)	0.943 (1.00)	0.435 (1.00)
Del Peak 26(22q13 32)	0 (0%)	73	0.0206 (1.00)	0.381 (1.00)	0.0415 (1.00)	1 (1.00)	0.455 (1.00)	0.463 (1.00)
Del Peak 27(Xq27 3)	0 (0%)	83	0.00774 (1.00)	0.126 (1.00)	0.216 (1.00)	0.336 (1.00)	0.601 (1.00)	0.36 (1.00)

'Amp Peak 2(1q22)' versus 'METHLYATION_CNMF'

P value = 0.000571 (Fisher's exact test), Q value = 0.18

Table S1. Gene #2: 'Amp Peak 2(1q22)' versus Molecular Subtype #2: 'METHLYATION_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	23	28	45
AMP PEAK 2(1Q22) CNV	10	23	39
AMP PEAK 2(1Q22) WILD-TYPE	13	5	6

Figure S1. Get High-res Image Gene #2: 'Amp Peak 2(1q22)' versus Molecular Subtype #2: 'METHLYATION_CNMF'

'Amp Peak 11(6p21.1)' versus 'METHLYATION_CNMF'

P value = 7.43e-05 (Fisher's exact test), Q value = 0.023

Table S2. Gene #11: 'Amp Peak 11(6p21.1)' versus Molecular Subtype #2: 'METHLYATION_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	23	28	45
AMP PEAK 11(6P21.1) CNV	2	12	28
AMP PEAK 11(6P21.1) WILD-TYPE	21	16	17

Figure S2. Get High-res Image Gene #11: 'Amp Peak 11(6p21.1)' versus Molecular Subtype #2: 'METHLYATION_CNMF'

'Amp Peak 14(8q13.1)' versus 'CN_CNMF'

P value = 4.22e-09 (Fisher's exact test), Q value = 1.3e-06

Table S3. Gene #14: 'Amp Peak 14(8q13.1)' versus Molecular Subtype #1: 'CN_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	28	36	33
AMP PEAK 14(8Q13.1) CNV	27	10	12
AMP PEAK 14(8Q13.1) WILD-TYPE	1	26	21

Figure S3. Get High-res Image Gene #14: 'Amp Peak 14(8q13.1)' versus Molecular Subtype #1: 'CN_CNMF'

'Amp Peak 15(8q24.13)' versus 'CN_CNMF'

P value = 1.8e-07 (Fisher's exact test), Q value = 5.7e-05

Table S4. Gene #15: 'Amp Peak 15(8q24.13)' versus Molecular Subtype #1: 'CN_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	28	36	33
AMP PEAK 15(8Q24.13) CNV	28	15	17
AMP PEAK 15(8Q24.13) WILD-TYPE	0	21	16

Figure S4. Get High-res Image Gene #15: 'Amp Peak 15(8q24.13)' versus Molecular Subtype #1: 'CN_CNMF'

'Amp Peak 18(12q23.1)' versus 'CN_CNMF'

P value = 0.00045 (Fisher's exact test), Q value = 0.14

Table S5. Gene #18: 'Amp Peak 18(12q23.1)' versus Molecular Subtype #1: 'CN_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	28	36	33
AMP PEAK 18(12Q23.1) CNV	5	1	13
AMP PEAK 18(12Q23.1) WILD-TYPE	23	35	20

Figure S5. Get High-res Image Gene #18: 'Amp Peak 18(12q23.1)' versus Molecular Subtype #1: 'CN_CNMF'

'Amp Peak 24(17q25.3)' versus 'CN_CNMF'

P value = 0.000453 (Fisher's exact test), Q value = 0.14

Table S6. Gene #24: 'Amp Peak 24(17q25.3)' versus Molecular Subtype #1: 'CN_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	28	36	33
AMP PEAK 24(17Q25.3) CNV	10	10	24
AMP PEAK 24(17Q25.3) WILD-TYPE	18	26	9

Figure S6. Get High-res Image Gene #24: 'Amp Peak 24(17q25.3)' versus Molecular Subtype #1: 'CN_CNMF'

'Del Peak 4(3p13)' versus 'MRNASEQ_CHIERARCHICAL'

P value = 0.000163 (Fisher's exact test), Q value = 0.051

Table S7. Gene #30: 'Del Peak 4(3p13)' versus Molecular Subtype #4: 'MRNASEQ_CHIERARCHICAL'

nPatients	CLUS_1	CLUS_2
ALL	29	40
DEL PEAK 4(3P13) CNV	11	1
DEL PEAK 4(3P13) WILD-TYPE	18	39

Figure S7. Get High-res Image Gene #30: 'Del Peak 4(3p13)' versus Molecular Subtype #4: 'MRNASEQ_CHIERARCHICAL'

'Del Peak 5(4q24)' versus 'CN_CNMF'

P value = 8.47e-05 (Fisher's exact test), Q value = 0.027

Table S8. Gene #31: 'Del Peak 5(4q24)' versus Molecular Subtype #1: 'CN_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	28	36	33
DEL PEAK 5(4Q24) CNV	13	6	22
DEL PEAK 5(4Q24) WILD-TYPE	15	30	11

Figure S8. Get High-res Image Gene #31: 'Del Peak 5(4q24)' versus Molecular Subtype #1: 'CN_CNMF'

'Del Peak 10(8p23.2)' versus 'CN_CNMF'

P value = 3.6e-07 (Fisher's exact test), Q value = 0.00011

Table S9. Gene #36: 'Del Peak 10(8p23.2)' versus Molecular Subtype #1: 'CN_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	28	36	33
DEL PEAK 10(8P23.2) CNV	27	12	21
DEL PEAK 10(8P23.2) WILD-TYPE	1	24	12

Figure S9. Get High-res Image Gene #36: 'Del Peak 10(8p23.2)' versus Molecular Subtype #1: 'CN_CNMF'

'Del Peak 21(16q23.1)' versus 'CN_CNMF'

P value = 0.00075 (Fisher's exact test), Q value = 0.23

Table S10. Gene #47: 'Del Peak 21(16q23.1)' versus Molecular Subtype #1: 'CN_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	28	36	33
DEL PEAK 21(16Q23.1) CNV	9	10	23
DEL PEAK 21(16Q23.1) WILD-TYPE	19	26	10

Figure S10. Get High-res Image Gene #47: 'Del Peak 21(16q23.1)' 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 = LIHC-TP.transferedmergedcluster.txt
Number of patients = 97
Number of copy number variation regions = 53
Number of molecular subtypes = 6
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

Chi-square test

For multi-class clinical features (nominal or ordinal), Chi-square tests (Greenwood and Nikulin 1996) were used to estimate the P values using the 'chisq.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] Greenwood and Nikulin, A guide to chi-squared testing, Wiley, New York. ISBN 047155779X (1996)

[3] 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)

[4] GISTIC_version2

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