Correlation between copy number variation genes and molecular subtypes

Cervical Squamous Cell Carcinoma (Primary solid tumor)

23 May 2013 | analyses__2013_05_23

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): Correlation between copy number variation genes and molecular subtypes. Broad Institute of MIT and Harvard. doi:10.7908/C1SJ1HKX

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 52 peak regions and 8 molecular subtypes across 126 patients, 11 significant findings detected with Q value < 0.25.

Amp Peak 4(2q32.3) cnvs correlated to 'CN_CNMF'.
Amp Peak 5(3q26.2) cnvs correlated to 'CN_CNMF'.
Amp Peak 6(3q28) cnvs correlated to 'CN_CNMF'.
Amp Peak 14(11q22.1) cnvs correlated to 'CN_CNMF'.
Del Peak 6(4q22.1) cnvs correlated to 'CN_CNMF'.
Del Peak 7(4q35.2) cnvs correlated to 'CN_CNMF'.
Del Peak 14(10q26.3) cnvs correlated to 'CN_CNMF'.
Del Peak 19(15q15.1) cnvs correlated to 'CN_CNMF'.
Del Peak 21(16q23.1) cnvs correlated to 'MRNASEQ_CNMF' and 'MRNASEQ_CHIERARCHICAL'.
Del Peak 23(17q25.3) cnvs correlated to 'METHLYATION_CNMF'.

Results

Overview of the results

Table 1. Get Full Table Overview of the association between significant copy number variation of 52 regions and 8 molecular subtypes. Shown in the table are P values (Q values). Thresholded by Q value < 0.25, 11 significant findings detected.


		Molecular subtypes	CN CNMF	METHLYATION CNMF	MRNASEQ CNMF	MRNASEQ CHIERARCHICAL	MIRSEQ CNMF	MIRSEQ CHIERARCHICAL	MIRSEQ MATURE CNMF	MIRSEQ MATURE CHIERARCHICAL
	nCNV (%)	nWild-Type	Fisher's exact test	Fisher's exact test	Fisher's exact test	Fisher's exact test	Fisher's exact test	Fisher's exact test	Fisher's exact test	Fisher's exact test
Del Peak 21(16q23 1)	0 (0%)	98	1 (1.00)	0.0278 (1.00)	0.000234 (0.0957)	3.45e-05 (0.0142)	0.0122 (1.00)	0.000849 (0.342)	0.00102 (0.408)	0.00194 (0.765)
Amp Peak 4(2q32 3)	0 (0%)	106	0.000238 (0.097)	0.0919 (1.00)	0.000645 (0.261)	0.00615 (1.00)	0.493 (1.00)	1 (1.00)	0.103 (1.00)	0.00495 (1.00)
Amp Peak 5(3q26 2)	0 (0%)	31	1.26e-06 (0.000522)	0.702 (1.00)	0.0931 (1.00)	0.332 (1.00)	0.0152 (1.00)	0.263 (1.00)	0.297 (1.00)	0.0114 (1.00)
Amp Peak 6(3q28)	0 (0%)	32	6.37e-07 (0.000265)	0.707 (1.00)	0.0492 (1.00)	0.363 (1.00)	0.0108 (1.00)	0.373 (1.00)	0.169 (1.00)	0.00706 (1.00)
Amp Peak 14(11q22 1)	0 (0%)	99	7.38e-05 (0.0303)	0.0584 (1.00)	0.0782 (1.00)	0.223 (1.00)	0.0713 (1.00)	0.0597 (1.00)	0.0419 (1.00)	0.173 (1.00)
Del Peak 6(4q22 1)	0 (0%)	87	1.5e-06 (0.00062)	0.169 (1.00)	0.0723 (1.00)	0.534 (1.00)	0.732 (1.00)	0.532 (1.00)	0.463 (1.00)	0.59 (1.00)
Del Peak 7(4q35 2)	0 (0%)	79	1.38e-05 (0.0057)	0.0876 (1.00)	0.0499 (1.00)	0.16 (1.00)	0.656 (1.00)	0.427 (1.00)	0.217 (1.00)	0.521 (1.00)
Del Peak 14(10q26 3)	0 (0%)	88	0.000133 (0.0545)	0.73 (1.00)	0.421 (1.00)	0.398 (1.00)	0.851 (1.00)	1 (1.00)	0.587 (1.00)	0.91 (1.00)
Del Peak 19(15q15 1)	0 (0%)	97	2.68e-05 (0.011)	0.378 (1.00)	0.303 (1.00)	0.292 (1.00)	0.0959 (1.00)	1 (1.00)	0.0494 (1.00)	0.224 (1.00)
Del Peak 23(17q25 3)	0 (0%)	104	0.0451 (1.00)	0.000537 (0.218)	0.0359 (1.00)	0.0345 (1.00)	0.0109 (1.00)	0.0204 (1.00)	0.0104 (1.00)	0.0824 (1.00)
Amp Peak 1(1q21 3)	0 (0%)	59	0.0103 (1.00)	0.0781 (1.00)	0.386 (1.00)	0.635 (1.00)	0.428 (1.00)	0.333 (1.00)	0.767 (1.00)	0.0888 (1.00)
Amp Peak 2(1q44)	0 (0%)	58	0.00905 (1.00)	0.746 (1.00)	0.573 (1.00)	1 (1.00)	0.914 (1.00)	0.436 (1.00)	0.146 (1.00)	0.499 (1.00)
Amp Peak 3(2p24 3)	0 (0%)	93	0.147 (1.00)	0.321 (1.00)	0.0605 (1.00)	0.0689 (1.00)	0.484 (1.00)	0.0819 (1.00)	0.0955 (1.00)	0.00325 (1.00)
Amp Peak 7(4q12)	0 (0%)	114	0.507 (1.00)	0.183 (1.00)	0.0826 (1.00)	0.00436 (1.00)	0.495 (1.00)	0.0428 (1.00)	0.316 (1.00)	0.439 (1.00)
Amp Peak 8(6p21 33)	0 (0%)	91	0.00495 (1.00)	0.0177 (1.00)	0.00286 (1.00)	0.0553 (1.00)	0.326 (1.00)	0.386 (1.00)	0.126 (1.00)	0.117 (1.00)
Amp Peak 9(6q12)	0 (0%)	102	0.342 (1.00)	0.203 (1.00)	0.143 (1.00)	0.00858 (1.00)	0.485 (1.00)	0.217 (1.00)	0.3 (1.00)	0.313 (1.00)
Amp Peak 10(8q24 21)	0 (0%)	73	0.00207 (0.815)	0.629 (1.00)	0.647 (1.00)	0.534 (1.00)	0.554 (1.00)	0.699 (1.00)	0.0607 (1.00)	0.492 (1.00)
Amp Peak 11(8q24 21)	0 (0%)	78	0.00432 (1.00)	0.272 (1.00)	0.705 (1.00)	0.386 (1.00)	0.314 (1.00)	0.69 (1.00)	0.104 (1.00)	0.657 (1.00)
Amp Peak 12(9p24 1)	0 (0%)	98	0.0587 (1.00)	0.543 (1.00)	0.806 (1.00)	0.528 (1.00)	0.479 (1.00)	0.351 (1.00)	0.191 (1.00)	0.412 (1.00)
Amp Peak 13(11q13 3)	0 (0%)	108	0.0384 (1.00)	0.728 (1.00)	0.0171 (1.00)	0.0291 (1.00)	0.658 (1.00)	0.785 (1.00)	0.221 (1.00)	0.851 (1.00)
Amp Peak 15(13q22 1)	0 (0%)	99	0.00534 (1.00)	0.42 (1.00)	0.205 (1.00)	0.224 (1.00)	0.157 (1.00)	0.813 (1.00)	0.461 (1.00)	0.143 (1.00)
Amp Peak 16(14q24 1)	0 (0%)	101	0.689 (1.00)	0.72 (1.00)	0.282 (1.00)	0.113 (1.00)	0.752 (1.00)	1 (1.00)	0.921 (1.00)	0.496 (1.00)
Amp Peak 17(15q26 3)	0 (0%)	96	0.00584 (1.00)	0.747 (1.00)	0.316 (1.00)	0.539 (1.00)	0.312 (1.00)	0.82 (1.00)	0.836 (1.00)	0.4 (1.00)
Amp Peak 18(16p13 2)	0 (0%)	99	0.0757 (1.00)	0.437 (1.00)	0.87 (1.00)	0.739 (1.00)	0.881 (1.00)	0.813 (1.00)	0.823 (1.00)	0.579 (1.00)
Amp Peak 19(16p13 13)	0 (0%)	96	0.0618 (1.00)	0.267 (1.00)	0.647 (1.00)	0.235 (1.00)	0.918 (1.00)	0.254 (1.00)	0.749 (1.00)	0.267 (1.00)
Amp Peak 20(17q12)	0 (0%)	105	0.0631 (1.00)	0.012 (1.00)	0.0126 (1.00)	0.0951 (1.00)	0.367 (1.00)	0.0202 (1.00)	0.0803 (1.00)	0.0106 (1.00)
Amp Peak 21(17q25 1)	0 (0%)	92	0.0113 (1.00)	0.0115 (1.00)	0.0411 (1.00)	0.429 (1.00)	0.631 (1.00)	0.276 (1.00)	0.0971 (1.00)	0.297 (1.00)
Amp Peak 22(19q13 31)	0 (0%)	83	0.0124 (1.00)	0.57 (1.00)	0.287 (1.00)	0.154 (1.00)	0.806 (1.00)	0.687 (1.00)	0.523 (1.00)	0.79 (1.00)
Amp Peak 23(20q11 21)	0 (0%)	65	0.000998 (0.401)	0.265 (1.00)	0.283 (1.00)	0.256 (1.00)	0.42 (1.00)	0.565 (1.00)	0.73 (1.00)	0.345 (1.00)
Amp Peak 24(Xq28)	0 (0%)	90	0.795 (1.00)	0.12 (1.00)	0.673 (1.00)	0.909 (1.00)	0.0331 (1.00)	0.521 (1.00)	0.0024 (0.932)	0.04 (1.00)
Del Peak 1(1p36 23)	0 (0%)	106	0.0829 (1.00)	0.00938 (1.00)	0.00125 (0.495)	0.0013 (0.514)	0.115 (1.00)	0.0149 (1.00)	0.0023 (0.904)	0.00236 (0.919)
Del Peak 2(1p13 1)	0 (0%)	114	0.75 (1.00)	0.693 (1.00)	1 (1.00)	1 (1.00)	0.395 (1.00)	0.345 (1.00)	0.217 (1.00)	0.865 (1.00)
Del Peak 3(2q22 1)	0 (0%)	104	0.0525 (1.00)	0.634 (1.00)	0.906 (1.00)	0.821 (1.00)	0.39 (1.00)	0.805 (1.00)	0.35 (1.00)	0.666 (1.00)
Del Peak 4(2q37 1)	0 (0%)	75	0.00431 (1.00)	0.023 (1.00)	0.201 (1.00)	0.333 (1.00)	0.156 (1.00)	0.00523 (1.00)	0.197 (1.00)	0.0353 (1.00)
Del Peak 5(3p11 1)	0 (0%)	75	0.000668 (0.27)	0.0413 (1.00)	0.39 (1.00)	0.00232 (0.908)	0.036 (1.00)	0.017 (1.00)	0.153 (1.00)	0.0433 (1.00)
Del Peak 8(5q14 3)	0 (0%)	90	0.0245 (1.00)	0.265 (1.00)	0.631 (1.00)	0.144 (1.00)	0.167 (1.00)	0.133 (1.00)	0.659 (1.00)	0.155 (1.00)
Del Peak 9(6p24 3)	0 (0%)	108	0.619 (1.00)	0.165 (1.00)	0.258 (1.00)	0.159 (1.00)	0.768 (1.00)	1 (1.00)	0.501 (1.00)	0.586 (1.00)
Del Peak 10(6p12 1)	0 (0%)	106	0.674 (1.00)	0.435 (1.00)	0.466 (1.00)	0.123 (1.00)	0.524 (1.00)	0.791 (1.00)	0.749 (1.00)	0.164 (1.00)
Del Peak 11(6q26)	0 (0%)	78	0.134 (1.00)	0.588 (1.00)	0.363 (1.00)	0.676 (1.00)	0.942 (1.00)	1 (1.00)	1 (1.00)	0.87 (1.00)
Del Peak 12(7q34)	0 (0%)	98	0.00527 (1.00)	0.632 (1.00)	0.12 (1.00)	0.668 (1.00)	0.204 (1.00)	0.642 (1.00)	0.416 (1.00)	0.504 (1.00)
Del Peak 13(10q23 31)	0 (0%)	87	0.0221 (1.00)	0.59 (1.00)	0.272 (1.00)	0.0197 (1.00)	0.941 (1.00)	1 (1.00)	0.885 (1.00)	0.884 (1.00)
Del Peak 15(11p15 1)	0 (0%)	86	0.301 (1.00)	0.0901 (1.00)	0.162 (1.00)	0.0665 (1.00)	0.43 (1.00)	0.219 (1.00)	0.426 (1.00)	0.633 (1.00)
Del Peak 16(11q25)	0 (0%)	52	0.00223 (0.877)	0.117 (1.00)	0.127 (1.00)	0.106 (1.00)	0.212 (1.00)	0.238 (1.00)	0.0192 (1.00)	0.268 (1.00)
Del Peak 17(13q13 3)	0 (0%)	74	0.144 (1.00)	0.176 (1.00)	0.398 (1.00)	0.807 (1.00)	0.118 (1.00)	0.0775 (1.00)	0.0186 (1.00)	0.382 (1.00)
Del Peak 18(14q32 31)	0 (0%)	101	0.0774 (1.00)	0.0116 (1.00)	0.00118 (0.469)	0.00122 (0.486)	0.0124 (1.00)	0.142 (1.00)	0.00271 (1.00)	0.0202 (1.00)
Del Peak 20(16q11 2)	0 (0%)	101	0.75 (1.00)	0.0445 (1.00)	0.0103 (1.00)	0.00812 (1.00)	0.0654 (1.00)	0.00302 (1.00)	0.0158 (1.00)	0.0212 (1.00)
Del Peak 22(17p12)	0 (0%)	84	0.0111 (1.00)	0.105 (1.00)	0.233 (1.00)	0.755 (1.00)	0.0702 (1.00)	0.153 (1.00)	0.206 (1.00)	0.743 (1.00)
Del Peak 24(19p13 3)	0 (0%)	87	0.00302 (1.00)	0.94 (1.00)	0.00295 (1.00)	0.0699 (1.00)	0.235 (1.00)	0.209 (1.00)	0.088 (1.00)	0.0978 (1.00)
Del Peak 25(20p12 1)	0 (0%)	109	0.846 (1.00)	0.405 (1.00)	0.746 (1.00)	1 (1.00)	0.552 (1.00)	1 (1.00)	0.215 (1.00)	0.674 (1.00)
Del Peak 26(21q21 1)	0 (0%)	99	0.0618 (1.00)	0.334 (1.00)	0.569 (1.00)	0.387 (1.00)	0.968 (1.00)	1 (1.00)	0.678 (1.00)	0.79 (1.00)
Del Peak 27(Xp11 3)	0 (0%)	89	0.00441 (1.00)	0.00277 (1.00)	0.211 (1.00)	0.192 (1.00)	0.00111 (0.445)	0.206 (1.00)	0.0805 (1.00)	0.0202 (1.00)
Del Peak 28(Xq21 33)	0 (0%)	99	0.0119 (1.00)	0.00292 (1.00)	0.164 (1.00)	0.0901 (1.00)	0.022 (1.00)	0.162 (1.00)	0.285 (1.00)	0.0989 (1.00)

'Amp Peak 4(2q32.3)' versus 'CN_CNMF'

P value = 0.000238 (Fisher's exact test), Q value = 0.097

Table S1. Gene #4: 'Amp Peak 4(2q32.3)' versus Molecular Subtype #1: 'CN_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	42	32	52
AMP PEAK 4(2Q32.3) CNV	9	10	1
AMP PEAK 4(2Q32.3) WILD-TYPE	33	22	51

Figure S1. Get High-res Image Gene #4: 'Amp Peak 4(2q32.3)' versus Molecular Subtype #1: 'CN_CNMF'

'Amp Peak 5(3q26.2)' versus 'CN_CNMF'

P value = 1.26e-06 (Fisher's exact test), Q value = 0.00052

Table S2. Gene #5: 'Amp Peak 5(3q26.2)' versus Molecular Subtype #1: 'CN_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	42	32	52
AMP PEAK 5(3Q26.2) CNV	42	20	33
AMP PEAK 5(3Q26.2) WILD-TYPE	0	12	19

Figure S2. Get High-res Image Gene #5: 'Amp Peak 5(3q26.2)' versus Molecular Subtype #1: 'CN_CNMF'

'Amp Peak 6(3q28)' versus 'CN_CNMF'

P value = 6.37e-07 (Fisher's exact test), Q value = 0.00026

Table S3. Gene #6: 'Amp Peak 6(3q28)' versus Molecular Subtype #1: 'CN_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	42	32	52
AMP PEAK 6(3Q28) CNV	42	19	33
AMP PEAK 6(3Q28) WILD-TYPE	0	13	19

Figure S3. Get High-res Image Gene #6: 'Amp Peak 6(3q28)' versus Molecular Subtype #1: 'CN_CNMF'

'Amp Peak 14(11q22.1)' versus 'CN_CNMF'

P value = 7.38e-05 (Fisher's exact test), Q value = 0.03

Table S4. Gene #14: 'Amp Peak 14(11q22.1)' versus Molecular Subtype #1: 'CN_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	42	32	52
AMP PEAK 14(11Q22.1) CNV	4	16	7
AMP PEAK 14(11Q22.1) WILD-TYPE	38	16	45

Figure S4. Get High-res Image Gene #14: 'Amp Peak 14(11q22.1)' versus Molecular Subtype #1: 'CN_CNMF'

'Del Peak 6(4q22.1)' versus 'CN_CNMF'

P value = 1.5e-06 (Fisher's exact test), Q value = 0.00062

Table S5. Gene #30: 'Del Peak 6(4q22.1)' versus Molecular Subtype #1: 'CN_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	42	32	52
DEL PEAK 6(4Q22.1) CNV	12	21	6
DEL PEAK 6(4Q22.1) WILD-TYPE	30	11	46

Figure S5. Get High-res Image Gene #30: 'Del Peak 6(4q22.1)' versus Molecular Subtype #1: 'CN_CNMF'

'Del Peak 7(4q35.2)' versus 'CN_CNMF'

P value = 1.38e-05 (Fisher's exact test), Q value = 0.0057

Table S6. Gene #31: 'Del Peak 7(4q35.2)' versus Molecular Subtype #1: 'CN_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	42	32	52
DEL PEAK 7(4Q35.2) CNV	13	23	11
DEL PEAK 7(4Q35.2) WILD-TYPE	29	9	41

Figure S6. Get High-res Image Gene #31: 'Del Peak 7(4q35.2)' versus Molecular Subtype #1: 'CN_CNMF'

'Del Peak 14(10q26.3)' versus 'CN_CNMF'

P value = 0.000133 (Fisher's exact test), Q value = 0.054

Table S7. Gene #38: 'Del Peak 14(10q26.3)' versus Molecular Subtype #1: 'CN_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	42	32	52
DEL PEAK 14(10Q26.3) CNV	11	19	8
DEL PEAK 14(10Q26.3) WILD-TYPE	31	13	44

Figure S7. Get High-res Image Gene #38: 'Del Peak 14(10q26.3)' versus Molecular Subtype #1: 'CN_CNMF'

'Del Peak 19(15q15.1)' versus 'CN_CNMF'

P value = 2.68e-05 (Fisher's exact test), Q value = 0.011

Table S8. Gene #43: 'Del Peak 19(15q15.1)' versus Molecular Subtype #1: 'CN_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	42	32	52
DEL PEAK 19(15Q15.1) CNV	7	17	5
DEL PEAK 19(15Q15.1) WILD-TYPE	35	15	47

Figure S8. Get High-res Image Gene #43: 'Del Peak 19(15q15.1)' versus Molecular Subtype #1: 'CN_CNMF'

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

P value = 0.000234 (Fisher's exact test), Q value = 0.096

Table S9. Gene #45: 'Del Peak 21(16q23.1)' versus Molecular Subtype #3: 'MRNASEQ_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	50	30	31
DEL PEAK 21(16Q23.1) CNV	3	9	13
DEL PEAK 21(16Q23.1) WILD-TYPE	47	21	18

Figure S9. Get High-res Image Gene #45: 'Del Peak 21(16q23.1)' versus Molecular Subtype #3: 'MRNASEQ_CNMF'

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

P value = 3.45e-05 (Fisher's exact test), Q value = 0.014

Table S10. Gene #45: 'Del Peak 21(16q23.1)' versus Molecular Subtype #4: 'MRNASEQ_CHIERARCHICAL'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	11	64	36
DEL PEAK 21(16Q23.1) CNV	6	5	14
DEL PEAK 21(16Q23.1) WILD-TYPE	5	59	22

Figure S10. Get High-res Image Gene #45: 'Del Peak 21(16q23.1)' versus Molecular Subtype #4: 'MRNASEQ_CHIERARCHICAL'

'Del Peak 23(17q25.3)' versus 'METHLYATION_CNMF'

P value = 0.000537 (Fisher's exact test), Q value = 0.22

Table S11. Gene #47: 'Del Peak 23(17q25.3)' versus Molecular Subtype #2: 'METHLYATION_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	52	41	33
DEL PEAK 23(17Q25.3) CNV	17	4	1
DEL PEAK 23(17Q25.3) WILD-TYPE	35	37	32

Figure S11. Get High-res Image Gene #47: 'Del Peak 23(17q25.3)' versus Molecular Subtype #2: 'METHLYATION_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 = CESC-TP.transferedmergedcluster.txt
Number of patients = 126
Number of copy number variation regions = 52
Number of molecular subtypes = 8
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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