Correlation between copy number variation genes (focal) and selected clinical features

Brain Lower Grade Glioma (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 (focal) and selected clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C1DR2SJT

Overview

Introduction

This pipeline computes the correlation between significant copy number variation (cnv focal) genes and selected clinical features.

Summary

Testing the association between copy number variation 43 arm-level results and 6 clinical features across 207 patients, 13 significant findings detected with Q value < 0.25.

Amp Peak 1(1q32.1) cnv correlated to 'AGE'.
Amp Peak 3(7p11.2) cnv correlated to 'AGE'.
Amp Peak 4(7q32.3) cnv correlated to 'AGE'.
Amp Peak 11(12q14.1) cnv correlated to 'Time to Death'.
Amp Peak 13(19q13.2) cnv correlated to 'Time to Death' and 'AGE'.
Del Peak 1(1p36.31) cnv correlated to 'HISTOLOGICAL.TYPE'.
Del Peak 2(1p32.3) cnv correlated to 'HISTOLOGICAL.TYPE'.
Del Peak 13(9p21.3) cnv correlated to 'Time to Death' and 'AGE'.
Del Peak 14(10q26.2) cnv correlated to 'Time to Death'.
Del Peak 20(14q24.3) cnv correlated to 'Time to Death'.
Del Peak 25(19q13.42) cnv correlated to 'HISTOLOGICAL.TYPE'.

Results

Overview of the results

Table 1. Get Full Table Overview of the association between significant copy number variation of 43 arm-level results and 6 clinical features. Shown in the table are P values (Q values). Thresholded by Q value < 0.25, 13 significant findings detected.


		Clinical Features	Time to Death	AGE	GENDER	KARNOFSKY PERFORMANCE SCORE	HISTOLOGICAL TYPE	RADIATIONS RADIATION REGIMENINDICATION
	nCNV (%)	nWild-Type	logrank test	t-test	Fisher's exact test	t-test	Fisher's exact test	Fisher's exact test
Amp Peak 13(19q13 2)	0 (0%)	192	6.78e-05 (0.0171)	0.00011 (0.0274)	0.792 (1.00)	0.508 (1.00)	0.396 (1.00)	0.585 (1.00)
Del Peak 13(9p21 3)	0 (0%)	133	3.01e-05 (0.00761)	0.000488 (0.12)	1 (1.00)	0.367 (1.00)	0.0451 (1.00)	0.0368 (1.00)
Amp Peak 1(1q32 1)	0 (0%)	184	0.0615 (1.00)	0.000116 (0.0288)	0.378 (1.00)	0.0855 (1.00)	0.182 (1.00)	0.653 (1.00)
Amp Peak 3(7p11 2)	0 (0%)	154	0.00366 (0.879)	0.000626 (0.154)	0.109 (1.00)	0.604 (1.00)	0.0547 (1.00)	1 (1.00)
Amp Peak 4(7q32 3)	0 (0%)	134	0.247 (1.00)	8.46e-05 (0.0212)	0.0283 (1.00)	0.844 (1.00)	0.384 (1.00)	0.655 (1.00)
Amp Peak 11(12q14 1)	0 (0%)	194	1.49e-05 (0.00378)	0.0516 (1.00)	0.564 (1.00)	0.466 (1.00)	0.117 (1.00)	1 (1.00)
Del Peak 1(1p36 31)	0 (0%)	127	0.93 (1.00)	0.00114 (0.278)	0.474 (1.00)	0.85 (1.00)	7.71e-13 (1.97e-10)	0.187 (1.00)
Del Peak 2(1p32 3)	0 (0%)	133	0.139 (1.00)	0.0029 (0.7)	0.771 (1.00)	0.952 (1.00)	7.56e-15 (1.94e-12)	0.0261 (1.00)
Del Peak 14(10q26 2)	0 (0%)	142	0.000151 (0.0374)	0.0104 (1.00)	0.0717 (1.00)	0.33 (1.00)	0.0167 (1.00)	0.761 (1.00)
Del Peak 20(14q24 3)	0 (0%)	159	0.000981 (0.24)	0.184 (1.00)	0.0455 (1.00)	0.994 (1.00)	0.0652 (1.00)	1 (1.00)
Del Peak 25(19q13 42)	0 (0%)	96	0.0266 (1.00)	0.629 (1.00)	0.888 (1.00)	0.566 (1.00)	9.51e-08 (2.42e-05)	1 (1.00)
Amp Peak 2(4q12)	0 (0%)	197	0.953 (1.00)	0.606 (1.00)	0.748 (1.00)	0.325 (1.00)	0.0461 (1.00)	1 (1.00)
Amp Peak 5(8q24 21)	0 (0%)	165	0.903 (1.00)	0.56 (1.00)	0.0837 (1.00)	0.332 (1.00)	0.011 (1.00)	0.11 (1.00)
Amp Peak 6(10p15 1)	0 (0%)	174	0.739 (1.00)	0.00528 (1.00)	0.127 (1.00)	0.636 (1.00)	0.00415 (0.989)	0.119 (1.00)
Amp Peak 7(10q11 21)	0 (0%)	203	0.782 (1.00)	0.692 (1.00)	0.636 (1.00)		0.0125 (1.00)	0.301 (1.00)
Amp Peak 8(11q23 3)	0 (0%)	172	0.605 (1.00)	0.0473 (1.00)	0.349 (1.00)	0.568 (1.00)	0.35 (1.00)	1 (1.00)
Amp Peak 9(12p13 32)	0 (0%)	175	0.899 (1.00)	0.0809 (1.00)	0.176 (1.00)	0.47 (1.00)	0.486 (1.00)	0.0774 (1.00)
Amp Peak 10(12p11 22)	0 (0%)	188	0.906 (1.00)	0.193 (1.00)	0.0521 (1.00)	0.448 (1.00)	0.297 (1.00)	0.0267 (1.00)
Amp Peak 12(19p13 3)	0 (0%)	159	0.828 (1.00)	0.0993 (1.00)	0.869 (1.00)	0.338 (1.00)	0.0146 (1.00)	0.735 (1.00)
Amp Peak 14(Xp22 33)	0 (0%)	193	0.579 (1.00)	0.877 (1.00)	1 (1.00)	0.611 (1.00)	0.00384 (0.917)	0.162 (1.00)
Amp Peak 15(Xq11 2)	0 (0%)	178	0.666 (1.00)	0.451 (1.00)	0.163 (1.00)	0.687 (1.00)	0.00489 (1.00)	0.305 (1.00)
Del Peak 3(1q43)	0 (0%)	195	0.942 (1.00)	0.546 (1.00)	0.369 (1.00)	0.244 (1.00)	0.491 (1.00)	1 (1.00)
Del Peak 4(2q37 3)	0 (0%)	176	0.818 (1.00)	0.0889 (1.00)	1 (1.00)	0.542 (1.00)	0.114 (1.00)	0.693 (1.00)
Del Peak 5(3p21 1)	0 (0%)	188	0.288 (1.00)	0.0149 (1.00)	0.634 (1.00)	0.674 (1.00)	0.362 (1.00)	0.0267 (1.00)
Del Peak 6(3q29)	0 (0%)	187	0.381 (1.00)	0.655 (1.00)	0.1 (1.00)	0.0446 (1.00)	0.159 (1.00)	0.812 (1.00)
Del Peak 7(4q33)	0 (0%)	147	0.614 (1.00)	0.813 (1.00)	0.164 (1.00)	0.532 (1.00)	0.133 (1.00)	0.0836 (1.00)
Del Peak 8(4q35 2)	0 (0%)	146	0.56 (1.00)	0.759 (1.00)	0.125 (1.00)	0.663 (1.00)	0.0924 (1.00)	0.117 (1.00)
Del Peak 9(5q35 2)	0 (0%)	180	0.0993 (1.00)	0.34 (1.00)	0.305 (1.00)	0.31 (1.00)	0.11 (1.00)	0.0324 (1.00)
Del Peak 10(6p24 1)	0 (0%)	190	0.0458 (1.00)	0.525 (1.00)	0.31 (1.00)	0.698 (1.00)	0.00129 (0.313)	0.298 (1.00)
Del Peak 11(6q24 3)	0 (0%)	177	0.0186 (1.00)	0.482 (1.00)	0.43 (1.00)	0.56 (1.00)	0.0243 (1.00)	0.418 (1.00)
Del Peak 12(8p23 2)	0 (0%)	197	0.362 (1.00)	0.514 (1.00)	1 (1.00)	0.249 (1.00)	0.133 (1.00)	0.514 (1.00)
Del Peak 15(11p15 5)	0 (0%)	164	0.381 (1.00)	0.0493 (1.00)	0.0598 (1.00)	0.671 (1.00)	0.00928 (1.00)	1 (1.00)
Del Peak 16(11q25)	0 (0%)	194	0.0051 (1.00)	0.944 (1.00)	0.246 (1.00)	0.864 (1.00)	0.623 (1.00)	1 (1.00)
Del Peak 17(12q24 11)	0 (0%)	180	0.861 (1.00)	0.286 (1.00)	0.305 (1.00)	0.34 (1.00)	0.11 (1.00)	0.143 (1.00)
Del Peak 18(13q14 2)	0 (0%)	145	0.462 (1.00)	0.853 (1.00)	0.648 (1.00)	0.0725 (1.00)	0.0745 (1.00)	0.217 (1.00)
Del Peak 19(13q34)	0 (0%)	159	0.361 (1.00)	0.528 (1.00)	0.506 (1.00)	0.433 (1.00)	0.551 (1.00)	0.617 (1.00)
Del Peak 21(15q21 3)	0 (0%)	181	0.15 (1.00)	0.34 (1.00)	1 (1.00)	0.212 (1.00)	0.646 (1.00)	0.83 (1.00)
Del Peak 22(17q25 3)	0 (0%)	196	0.606 (1.00)	0.454 (1.00)	0.761 (1.00)	0.731 (1.00)	1 (1.00)	0.343 (1.00)
Del Peak 23(18p11 32)	0 (0%)	178	0.822 (1.00)	0.852 (1.00)	0.225 (1.00)	0.349 (1.00)	0.875 (1.00)	0.15 (1.00)
Del Peak 24(18q23)	0 (0%)	175	0.722 (1.00)	0.383 (1.00)	0.699 (1.00)	0.843 (1.00)	0.876 (1.00)	0.845 (1.00)
Del Peak 26(22q13 31)	0 (0%)	178	0.116 (1.00)	0.281 (1.00)	0.319 (1.00)	0.733 (1.00)	0.0023 (0.556)	0.305 (1.00)
Del Peak 27(Xp22 31)	0 (0%)	159	0.54 (1.00)	0.489 (1.00)	0.319 (1.00)	0.675 (1.00)	0.831 (1.00)	0.868 (1.00)
Del Peak 28(Xq21 1)	0 (0%)	178	0.582 (1.00)	0.233 (1.00)	0.55 (1.00)	0.957 (1.00)	0.206 (1.00)	0.838 (1.00)

'Amp Peak 1(1q32.1)' versus 'AGE'

P value = 0.000116 (t-test), Q value = 0.029

Table S1. Gene #1: 'Amp Peak 1(1q32.1)' versus Clinical Feature #2: 'AGE'

	nPatients	Mean (Std.Dev)
ALL	207	43.1 (13.4)
AMP PEAK 1(1Q32.1) CNV	23	53.2 (11.4)
AMP PEAK 1(1Q32.1) WILD-TYPE	184	41.8 (13.1)

Figure S1. Get High-res Image Gene #1: 'Amp Peak 1(1q32.1)' versus Clinical Feature #2: 'AGE'

'Amp Peak 3(7p11.2)' versus 'AGE'

P value = 0.000626 (t-test), Q value = 0.15

Table S2. Gene #3: 'Amp Peak 3(7p11.2)' versus Clinical Feature #2: 'AGE'

	nPatients	Mean (Std.Dev)
ALL	207	43.1 (13.4)
AMP PEAK 3(7P11.2) CNV	53	48.7 (13.4)
AMP PEAK 3(7P11.2) WILD-TYPE	154	41.2 (12.9)

Figure S2. Get High-res Image Gene #3: 'Amp Peak 3(7p11.2)' versus Clinical Feature #2: 'AGE'

'Amp Peak 4(7q32.3)' versus 'AGE'

P value = 8.46e-05 (t-test), Q value = 0.021

Table S3. Gene #4: 'Amp Peak 4(7q32.3)' versus Clinical Feature #2: 'AGE'

	nPatients	Mean (Std.Dev)
ALL	207	43.1 (13.4)
AMP PEAK 4(7Q32.3) CNV	73	48.1 (13.1)
AMP PEAK 4(7Q32.3) WILD-TYPE	134	40.4 (12.9)

Figure S3. Get High-res Image Gene #4: 'Amp Peak 4(7q32.3)' versus Clinical Feature #2: 'AGE'

'Amp Peak 11(12q14.1)' versus 'Time to Death'

P value = 1.49e-05 (logrank test), Q value = 0.0038

Table S4. Gene #11: 'Amp Peak 11(12q14.1)' versus Clinical Feature #1: 'Time to Death'

	nPatients	nDeath	Duration Range (Median), Month
ALL	206	51	0.0 - 211.2 (13.4)
AMP PEAK 11(12Q14.1) CNV	13	9	1.2 - 80.0 (12.4)
AMP PEAK 11(12Q14.1) WILD-TYPE	193	42	0.0 - 211.2 (13.4)

Figure S4. Get High-res Image Gene #11: 'Amp Peak 11(12q14.1)' versus Clinical Feature #1: 'Time to Death'

'Amp Peak 13(19q13.2)' versus 'Time to Death'

P value = 6.78e-05 (logrank test), Q value = 0.017

Table S5. Gene #13: 'Amp Peak 13(19q13.2)' versus Clinical Feature #1: 'Time to Death'

	nPatients	nDeath	Duration Range (Median), Month
ALL	206	51	0.0 - 211.2 (13.4)
AMP PEAK 13(19Q13.2) CNV	15	6	0.0 - 43.9 (10.6)
AMP PEAK 13(19Q13.2) WILD-TYPE	191	45	0.1 - 211.2 (14.3)

Figure S5. Get High-res Image Gene #13: 'Amp Peak 13(19q13.2)' versus Clinical Feature #1: 'Time to Death'

'Amp Peak 13(19q13.2)' versus 'AGE'

P value = 0.00011 (t-test), Q value = 0.027

Table S6. Gene #13: 'Amp Peak 13(19q13.2)' versus Clinical Feature #2: 'AGE'

	nPatients	Mean (Std.Dev)
ALL	207	43.1 (13.4)
AMP PEAK 13(19Q13.2) CNV	15	53.1 (8.0)
AMP PEAK 13(19Q13.2) WILD-TYPE	192	42.3 (13.5)

Figure S6. Get High-res Image Gene #13: 'Amp Peak 13(19q13.2)' versus Clinical Feature #2: 'AGE'

'Del Peak 1(1p36.31)' versus 'HISTOLOGICAL.TYPE'

P value = 7.71e-13 (Fisher's exact test), Q value = 2e-10

Table S7. Gene #16: 'Del Peak 1(1p36.31)' versus Clinical Feature #5: 'HISTOLOGICAL.TYPE'

nPatients	ASTROCYTOMA	OLIGOASTROCYTOMA	OLIGODENDROGLIOMA
ALL	63	54	89
DEL PEAK 1(1P36.31) CNV	9	11	60
DEL PEAK 1(1P36.31) WILD-TYPE	54	43	29

Figure S7. Get High-res Image Gene #16: 'Del Peak 1(1p36.31)' versus Clinical Feature #5: 'HISTOLOGICAL.TYPE'

'Del Peak 2(1p32.3)' versus 'HISTOLOGICAL.TYPE'

P value = 7.56e-15 (Fisher's exact test), Q value = 1.9e-12

Table S8. Gene #17: 'Del Peak 2(1p32.3)' versus Clinical Feature #5: 'HISTOLOGICAL.TYPE'

nPatients	ASTROCYTOMA	OLIGOASTROCYTOMA	OLIGODENDROGLIOMA
ALL	63	54	89
DEL PEAK 2(1P32.3) CNV	7	8	59
DEL PEAK 2(1P32.3) WILD-TYPE	56	46	30

Figure S8. Get High-res Image Gene #17: 'Del Peak 2(1p32.3)' versus Clinical Feature #5: 'HISTOLOGICAL.TYPE'

'Del Peak 13(9p21.3)' versus 'Time to Death'

P value = 3.01e-05 (logrank test), Q value = 0.0076

Table S9. Gene #28: 'Del Peak 13(9p21.3)' versus Clinical Feature #1: 'Time to Death'

	nPatients	nDeath	Duration Range (Median), Month
ALL	206	51	0.0 - 211.2 (13.4)
DEL PEAK 13(9P21.3) CNV	73	26	0.1 - 117.4 (14.7)
DEL PEAK 13(9P21.3) WILD-TYPE	133	25	0.0 - 211.2 (13.4)

Figure S9. Get High-res Image Gene #28: 'Del Peak 13(9p21.3)' versus Clinical Feature #1: 'Time to Death'

'Del Peak 13(9p21.3)' versus 'AGE'

P value = 0.000488 (t-test), Q value = 0.12

Table S10. Gene #28: 'Del Peak 13(9p21.3)' versus Clinical Feature #2: 'AGE'

	nPatients	Mean (Std.Dev)
ALL	207	43.1 (13.4)
DEL PEAK 13(9P21.3) CNV	74	47.5 (13.2)
DEL PEAK 13(9P21.3) WILD-TYPE	133	40.7 (13.0)

Figure S10. Get High-res Image Gene #28: 'Del Peak 13(9p21.3)' versus Clinical Feature #2: 'AGE'

'Del Peak 14(10q26.2)' versus 'Time to Death'

P value = 0.000151 (logrank test), Q value = 0.037

Table S11. Gene #29: 'Del Peak 14(10q26.2)' versus Clinical Feature #1: 'Time to Death'

	nPatients	nDeath	Duration Range (Median), Month
ALL	206	51	0.0 - 211.2 (13.4)
DEL PEAK 14(10Q26.2) CNV	65	29	0.1 - 156.2 (12.4)
DEL PEAK 14(10Q26.2) WILD-TYPE	141	22	0.0 - 211.2 (14.3)

Figure S11. Get High-res Image Gene #29: 'Del Peak 14(10q26.2)' versus Clinical Feature #1: 'Time to Death'

'Del Peak 20(14q24.3)' versus 'Time to Death'

P value = 0.000981 (logrank test), Q value = 0.24

Table S12. Gene #35: 'Del Peak 20(14q24.3)' versus Clinical Feature #1: 'Time to Death'

	nPatients	nDeath	Duration Range (Median), Month
ALL	206	51	0.0 - 211.2 (13.4)
DEL PEAK 20(14Q24.3) CNV	48	22	0.2 - 130.8 (17.4)
DEL PEAK 20(14Q24.3) WILD-TYPE	158	29	0.0 - 211.2 (12.4)

Figure S12. Get High-res Image Gene #35: 'Del Peak 20(14q24.3)' versus Clinical Feature #1: 'Time to Death'

'Del Peak 25(19q13.42)' versus 'HISTOLOGICAL.TYPE'

P value = 9.51e-08 (Fisher's exact test), Q value = 2.4e-05

Table S13. Gene #40: 'Del Peak 25(19q13.42)' versus Clinical Feature #5: 'HISTOLOGICAL.TYPE'

nPatients	ASTROCYTOMA	OLIGOASTROCYTOMA	OLIGODENDROGLIOMA
ALL	63	54	89
DEL PEAK 25(19Q13.42) CNV	20	23	67
DEL PEAK 25(19Q13.42) WILD-TYPE	43	31	22

Figure S13. Get High-res Image Gene #40: 'Del Peak 25(19q13.42)' versus Clinical Feature #5: 'HISTOLOGICAL.TYPE'

Methods & Data

Input

Mutation data file = all_lesions.conf_99.cnv.cluster.txt
Clinical data file = LGG-TP.clin.merged.picked.txt
Number of patients = 207
Number of significantly arm-level cnvs = 43
Number of selected clinical features = 6
Exclude genes that fewer than K tumors have mutations, K = 3

Survival analysis

For survival clinical features, the Kaplan-Meier survival curves of tumors with and without gene mutations were plotted and the statistical significance P values were estimated by logrank test (Bland and Altman 2004) using the 'survdiff' function in R

Student's t-test analysis

For continuous numerical clinical features, two-tailed Student's t test with unequal variance (Lehmann and Romano 2005) was applied to compare the clinical values between tumors with and without gene mutations using 't.test' function in R

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] Bland and Altman, Statistics notes: The logrank test, BMJ 328(7447):1073 (2004)

[2] Lehmann and Romano, Testing Statistical Hypotheses (3E ed.), New York: Springer. ISBN 0387988645 (2005)

[3] 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)

[4] 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)

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