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

Kidney Renal Clear 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 (focal) and selected clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C1TD9VCB

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 32 arm-level results and 8 clinical features across 493 patients, 19 significant findings detected with Q value < 0.25.

Amp Peak 3(3q26.32) cnv correlated to 'DISTANT.METASTASIS' and 'NEOPLASM.DISEASESTAGE'.
Amp Peak 7(8q24.22) cnv correlated to 'NEOPLASM.DISEASESTAGE'.
Del Peak 9(3q11.2) cnv correlated to 'GENDER'.
Del Peak 10(3q21.3) cnv correlated to 'GENDER'.
Del Peak 11(4q34.3) cnv correlated to 'Time to Death' and 'NEOPLASM.DISEASESTAGE'.
Del Peak 15(9p23) cnv correlated to 'Time to Death', 'DISTANT.METASTASIS', and 'NEOPLASM.DISEASESTAGE'.
Del Peak 16(9p21.3) cnv correlated to 'Time to Death', 'GENDER', 'DISTANT.METASTASIS', and 'NEOPLASM.DISEASESTAGE'.
Del Peak 18(13q13.3) cnv correlated to 'Time to Death' and 'NEOPLASM.DISEASESTAGE'.
Del Peak 19(14q31.1) cnv correlated to 'DISTANT.METASTASIS', 'LYMPH.NODE.METASTASIS', and 'NEOPLASM.DISEASESTAGE'.

Results

Overview of the results

Table 1. Get Full Table Overview of the association between significant copy number variation of 32 arm-level results and 8 clinical features. Shown in the table are P values (Q values). Thresholded by Q value < 0.25, 19 significant findings detected.


		Clinical Features	Time to Death	AGE	GENDER	KARNOFSKY PERFORMANCE SCORE	DISTANT METASTASIS	LYMPH NODE METASTASIS	TUMOR STAGECODE	NEOPLASM DISEASESTAGE
	nCNV (%)	nWild-Type	logrank test	t-test	Fisher's exact test	t-test	Fisher's exact test	Fisher's exact test	t-test	Fisher's exact test
Del Peak 16(9p21 3)	0 (0%)	341	2.03e-06 (0.000445)	0.0261 (1.00)	0.00069 (0.144)	0.656 (1.00)	6.93e-05 (0.0148)	0.105 (1.00)		1.02e-08 (2.27e-06)
Del Peak 15(9p23)	0 (0%)	349	0.000138 (0.0292)	0.0136 (1.00)	0.0018 (0.362)	0.656 (1.00)	0.000876 (0.18)	0.122 (1.00)		1.64e-06 (0.000361)
Del Peak 19(14q31 1)	0 (0%)	275	0.00179 (0.361)	0.055 (1.00)	0.296 (1.00)	0.0872 (1.00)	0.00101 (0.208)	0.000371 (0.0779)		1.48e-05 (0.0032)
Amp Peak 3(3q26 32)	0 (0%)	413	0.156 (1.00)	0.903 (1.00)	0.442 (1.00)	0.152 (1.00)	7.09e-05 (0.0151)	0.00823 (1.00)		2.97e-05 (0.00639)
Del Peak 11(4q34 3)	0 (0%)	417	0.000557 (0.117)	0.568 (1.00)	0.433 (1.00)	0.0261 (1.00)	0.00862 (1.00)	0.354 (1.00)		2.41e-06 (0.000526)
Del Peak 18(13q13 3)	0 (0%)	417	0.000848 (0.175)	0.884 (1.00)	0.794 (1.00)	0.748 (1.00)	0.0377 (1.00)	0.601 (1.00)		0.000129 (0.0274)
Amp Peak 7(8q24 22)	0 (0%)	420	0.0527 (1.00)	0.0214 (1.00)	0.11 (1.00)	0.297 (1.00)	0.053 (1.00)	0.923 (1.00)		0.00122 (0.249)
Del Peak 9(3q11 2)	0 (0%)	343	0.635 (1.00)	0.0111 (1.00)	3.95e-08 (8.73e-06)	0.749 (1.00)	0.591 (1.00)	0.562 (1.00)		0.613 (1.00)
Del Peak 10(3q21 3)	0 (0%)	390	0.846 (1.00)	0.00205 (0.41)	7.86e-06 (0.00171)	0.0875 (1.00)	0.879 (1.00)	0.185 (1.00)		0.424 (1.00)
Amp Peak 1(1q24 1)	0 (0%)	433	0.2 (1.00)	0.164 (1.00)	0.666 (1.00)	0.499 (1.00)	0.339 (1.00)	0.111 (1.00)		0.339 (1.00)
Amp Peak 2(1q32 1)	0 (0%)	434	0.437 (1.00)	0.0725 (1.00)	0.771 (1.00)	0.499 (1.00)	0.703 (1.00)	0.653 (1.00)		0.234 (1.00)
Amp Peak 4(4q32 1)	0 (0%)	479	0.0584 (1.00)	0.416 (1.00)	0.258 (1.00)	0.411 (1.00)	0.462 (1.00)	0.0499 (1.00)		0.431 (1.00)
Amp Peak 5(5q35 1)	0 (0%)	182	0.0454 (1.00)	0.0923 (1.00)	0.141 (1.00)	0.944 (1.00)	0.366 (1.00)	0.499 (1.00)		0.557 (1.00)
Amp Peak 6(7q36 3)	0 (0%)	330	0.724 (1.00)	0.806 (1.00)	0.0352 (1.00)	0.57 (1.00)	0.00523 (1.00)	0.428 (1.00)		0.0198 (1.00)
Amp Peak 8(10p14)	0 (0%)	477	0.234 (1.00)	0.423 (1.00)	0.594 (1.00)	0.887 (1.00)	0.288 (1.00)	0.0682 (1.00)		0.129 (1.00)
Amp Peak 9(17q24 3)	0 (0%)	456	0.0512 (1.00)	0.0662 (1.00)	0.858 (1.00)	0.471 (1.00)	0.244 (1.00)	0.535 (1.00)		0.739 (1.00)
Amp Peak 10(Xp22 2)	0 (0%)	458	0.468 (1.00)	0.676 (1.00)	0.854 (1.00)	0.726 (1.00)	0.0897 (1.00)	0.177 (1.00)		0.0176 (1.00)
Amp Peak 11(Xp11 4)	0 (0%)	457	0.759 (1.00)	0.712 (1.00)	0.857 (1.00)	0.726 (1.00)	0.0509 (1.00)	0.276 (1.00)		0.00905 (1.00)
Amp Peak 12(Xq11 2)	0 (0%)	461	0.803 (1.00)	0.145 (1.00)	0.706 (1.00)	0.726 (1.00)	0.31 (1.00)	0.216 (1.00)		0.103 (1.00)
Amp Peak 13(Xq28)	0 (0%)	456	0.631 (1.00)	0.805 (1.00)	0.474 (1.00)	0.726 (1.00)	0.34 (1.00)	0.053 (1.00)		0.352 (1.00)
Del Peak 1(1p36 23)	0 (0%)	395	0.0495 (1.00)	0.123 (1.00)	0.123 (1.00)	0.284 (1.00)	0.0844 (1.00)	0.829 (1.00)		0.202 (1.00)
Del Peak 2(1p31 1)	0 (0%)	421	0.219 (1.00)	0.0726 (1.00)	0.016 (1.00)	0.284 (1.00)	0.294 (1.00)	0.765 (1.00)		0.428 (1.00)
Del Peak 3(1q43)	0 (0%)	455	0.704 (1.00)	0.335 (1.00)	1 (1.00)		1 (1.00)	0.589 (1.00)		0.694 (1.00)
Del Peak 4(2q37 3)	0 (0%)	445	0.673 (1.00)	0.63 (1.00)	0.153 (1.00)		0.402 (1.00)	0.952 (1.00)		0.622 (1.00)
Del Peak 5(3p25 3)	0 (0%)	61	0.783 (1.00)	0.788 (1.00)	0.569 (1.00)	0.0817 (1.00)	0.707 (1.00)	0.553 (1.00)		0.0266 (1.00)
Del Peak 6(3p21 32)	0 (0%)	58	0.498 (1.00)	0.704 (1.00)	0.772 (1.00)	0.0817 (1.00)	0.333 (1.00)	0.631 (1.00)		0.00141 (0.286)
Del Peak 7(3p12 3)	0 (0%)	182	0.69 (1.00)	0.762 (1.00)	0.00441 (0.874)	0.944 (1.00)	0.608 (1.00)	0.609 (1.00)		0.405 (1.00)
Del Peak 8(3p12 2)	0 (0%)	210	0.614 (1.00)	0.761 (1.00)	0.00221 (0.441)	0.741 (1.00)	0.53 (1.00)	0.779 (1.00)		0.609 (1.00)
Del Peak 12(6q26)	0 (0%)	351	0.565 (1.00)	0.287 (1.00)	0.012 (1.00)	0.256 (1.00)	0.41 (1.00)	0.0069 (1.00)		0.281 (1.00)
Del Peak 13(6q26)	0 (0%)	351	0.589 (1.00)	0.226 (1.00)	0.00648 (1.00)	0.256 (1.00)	0.41 (1.00)	0.0069 (1.00)		0.281 (1.00)
Del Peak 14(8p23 2)	0 (0%)	347	0.0385 (1.00)	0.139 (1.00)	0.256 (1.00)	0.893 (1.00)	0.055 (1.00)	0.48 (1.00)		0.119 (1.00)
Del Peak 17(10q23 31)	0 (0%)	403	0.217 (1.00)	0.209 (1.00)	0.0272 (1.00)	0.764 (1.00)	0.333 (1.00)	0.549 (1.00)		0.0187 (1.00)

'Amp Peak 3(3q26.32)' versus 'DISTANT.METASTASIS'

P value = 7.09e-05 (Fisher's exact test), Q value = 0.015

Table S1. Gene #3: 'Amp Peak 3(3q26.32)' versus Clinical Feature #5: 'DISTANT.METASTASIS'

nPatients	M0	M1
ALL	417	76
AMP PEAK 3(3Q26.32) CNV	55	25
AMP PEAK 3(3Q26.32) WILD-TYPE	362	51

Figure S1. Get High-res Image Gene #3: 'Amp Peak 3(3q26.32)' versus Clinical Feature #5: 'DISTANT.METASTASIS'

'Amp Peak 3(3q26.32)' versus 'NEOPLASM.DISEASESTAGE'

P value = 2.97e-05 (Fisher's exact test), Q value = 0.0064

Table S2. Gene #3: 'Amp Peak 3(3q26.32)' versus Clinical Feature #8: 'NEOPLASM.DISEASESTAGE'

nPatients	STAGE I	STAGE II	STAGE III	STAGE IV
ALL	237	53	126	77
AMP PEAK 3(3Q26.32) CNV	23	6	26	25
AMP PEAK 3(3Q26.32) WILD-TYPE	214	47	100	52

Figure S2. Get High-res Image Gene #3: 'Amp Peak 3(3q26.32)' versus Clinical Feature #8: 'NEOPLASM.DISEASESTAGE'

'Amp Peak 7(8q24.22)' versus 'NEOPLASM.DISEASESTAGE'

P value = 0.00122 (Fisher's exact test), Q value = 0.25

Table S3. Gene #7: 'Amp Peak 7(8q24.22)' versus Clinical Feature #8: 'NEOPLASM.DISEASESTAGE'

nPatients	STAGE I	STAGE II	STAGE III	STAGE IV
ALL	237	53	126	77
AMP PEAK 7(8Q24.22) CNV	20	10	26	17
AMP PEAK 7(8Q24.22) WILD-TYPE	217	43	100	60

Figure S3. Get High-res Image Gene #7: 'Amp Peak 7(8q24.22)' versus Clinical Feature #8: 'NEOPLASM.DISEASESTAGE'

'Del Peak 9(3q11.2)' versus 'GENDER'

P value = 3.95e-08 (Fisher's exact test), Q value = 8.7e-06

Table S4. Gene #22: 'Del Peak 9(3q11.2)' versus Clinical Feature #3: 'GENDER'

nPatients	FEMALE	MALE
ALL	171	322
DEL PEAK 9(3Q11.2) CNV	26	124
DEL PEAK 9(3Q11.2) WILD-TYPE	145	198

Figure S4. Get High-res Image Gene #22: 'Del Peak 9(3q11.2)' versus Clinical Feature #3: 'GENDER'

'Del Peak 10(3q21.3)' versus 'GENDER'

P value = 7.86e-06 (Fisher's exact test), Q value = 0.0017

Table S5. Gene #23: 'Del Peak 10(3q21.3)' versus Clinical Feature #3: 'GENDER'

nPatients	FEMALE	MALE
ALL	171	322
DEL PEAK 10(3Q21.3) CNV	17	86
DEL PEAK 10(3Q21.3) WILD-TYPE	154	236

Figure S5. Get High-res Image Gene #23: 'Del Peak 10(3q21.3)' versus Clinical Feature #3: 'GENDER'

'Del Peak 11(4q34.3)' versus 'Time to Death'

P value = 0.000557 (logrank test), Q value = 0.12

Table S6. Gene #24: 'Del Peak 11(4q34.3)' versus Clinical Feature #1: 'Time to Death'

	nPatients	nDeath	Duration Range (Median), Month
ALL	490	158	0.1 - 111.0 (35.2)
DEL PEAK 11(4Q34.3) CNV	76	38	0.2 - 91.4 (35.1)
DEL PEAK 11(4Q34.3) WILD-TYPE	414	120	0.1 - 111.0 (35.2)

Figure S6. Get High-res Image Gene #24: 'Del Peak 11(4q34.3)' versus Clinical Feature #1: 'Time to Death'

'Del Peak 11(4q34.3)' versus 'NEOPLASM.DISEASESTAGE'

P value = 2.41e-06 (Fisher's exact test), Q value = 0.00053

Table S7. Gene #24: 'Del Peak 11(4q34.3)' versus Clinical Feature #8: 'NEOPLASM.DISEASESTAGE'

nPatients	STAGE I	STAGE II	STAGE III	STAGE IV
ALL	237	53	126	77
DEL PEAK 11(4Q34.3) CNV	18	6	30	22
DEL PEAK 11(4Q34.3) WILD-TYPE	219	47	96	55

Figure S7. Get High-res Image Gene #24: 'Del Peak 11(4q34.3)' versus Clinical Feature #8: 'NEOPLASM.DISEASESTAGE'

'Del Peak 15(9p23)' versus 'Time to Death'

P value = 0.000138 (logrank test), Q value = 0.029

Table S8. Gene #28: 'Del Peak 15(9p23)' versus Clinical Feature #1: 'Time to Death'

	nPatients	nDeath	Duration Range (Median), Month
ALL	490	158	0.1 - 111.0 (35.2)
DEL PEAK 15(9P23) CNV	143	65	0.2 - 109.9 (36.1)
DEL PEAK 15(9P23) WILD-TYPE	347	93	0.1 - 111.0 (34.6)

Figure S8. Get High-res Image Gene #28: 'Del Peak 15(9p23)' versus Clinical Feature #1: 'Time to Death'

'Del Peak 15(9p23)' versus 'DISTANT.METASTASIS'

P value = 0.000876 (Fisher's exact test), Q value = 0.18

Table S9. Gene #28: 'Del Peak 15(9p23)' versus Clinical Feature #5: 'DISTANT.METASTASIS'

nPatients	M0	M1
ALL	417	76
DEL PEAK 15(9P23) CNV	109	35
DEL PEAK 15(9P23) WILD-TYPE	308	41

Figure S9. Get High-res Image Gene #28: 'Del Peak 15(9p23)' versus Clinical Feature #5: 'DISTANT.METASTASIS'

'Del Peak 15(9p23)' versus 'NEOPLASM.DISEASESTAGE'

P value = 1.64e-06 (Fisher's exact test), Q value = 0.00036

Table S10. Gene #28: 'Del Peak 15(9p23)' versus Clinical Feature #8: 'NEOPLASM.DISEASESTAGE'

nPatients	STAGE I	STAGE II	STAGE III	STAGE IV
ALL	237	53	126	77
DEL PEAK 15(9P23) CNV	47	11	50	36
DEL PEAK 15(9P23) WILD-TYPE	190	42	76	41

Figure S10. Get High-res Image Gene #28: 'Del Peak 15(9p23)' versus Clinical Feature #8: 'NEOPLASM.DISEASESTAGE'

'Del Peak 16(9p21.3)' versus 'Time to Death'

P value = 2.03e-06 (logrank test), Q value = 0.00044

Table S11. Gene #29: 'Del Peak 16(9p21.3)' versus Clinical Feature #1: 'Time to Death'

	nPatients	nDeath	Duration Range (Median), Month
ALL	490	158	0.1 - 111.0 (35.2)
DEL PEAK 16(9P21.3) CNV	152	72	0.2 - 109.9 (31.5)
DEL PEAK 16(9P21.3) WILD-TYPE	338	86	0.1 - 111.0 (36.2)

Figure S11. Get High-res Image Gene #29: 'Del Peak 16(9p21.3)' versus Clinical Feature #1: 'Time to Death'

'Del Peak 16(9p21.3)' versus 'GENDER'

P value = 0.00069 (Fisher's exact test), Q value = 0.14

Table S12. Gene #29: 'Del Peak 16(9p21.3)' versus Clinical Feature #3: 'GENDER'

nPatients	FEMALE	MALE
ALL	171	322
DEL PEAK 16(9P21.3) CNV	36	116
DEL PEAK 16(9P21.3) WILD-TYPE	135	206

Figure S12. Get High-res Image Gene #29: 'Del Peak 16(9p21.3)' versus Clinical Feature #3: 'GENDER'

'Del Peak 16(9p21.3)' versus 'DISTANT.METASTASIS'

P value = 6.93e-05 (Fisher's exact test), Q value = 0.015

Table S13. Gene #29: 'Del Peak 16(9p21.3)' versus Clinical Feature #5: 'DISTANT.METASTASIS'

nPatients	M0	M1
ALL	417	76
DEL PEAK 16(9P21.3) CNV	113	39
DEL PEAK 16(9P21.3) WILD-TYPE	304	37

Figure S13. Get High-res Image Gene #29: 'Del Peak 16(9p21.3)' versus Clinical Feature #5: 'DISTANT.METASTASIS'

'Del Peak 16(9p21.3)' versus 'NEOPLASM.DISEASESTAGE'

P value = 1.02e-08 (Fisher's exact test), Q value = 2.3e-06

Table S14. Gene #29: 'Del Peak 16(9p21.3)' versus Clinical Feature #8: 'NEOPLASM.DISEASESTAGE'

nPatients	STAGE I	STAGE II	STAGE III	STAGE IV
ALL	237	53	126	77
DEL PEAK 16(9P21.3) CNV	48	10	54	40
DEL PEAK 16(9P21.3) WILD-TYPE	189	43	72	37

Figure S14. Get High-res Image Gene #29: 'Del Peak 16(9p21.3)' versus Clinical Feature #8: 'NEOPLASM.DISEASESTAGE'

'Del Peak 18(13q13.3)' versus 'Time to Death'

P value = 0.000848 (logrank test), Q value = 0.18

Table S15. Gene #31: 'Del Peak 18(13q13.3)' versus Clinical Feature #1: 'Time to Death'

	nPatients	nDeath	Duration Range (Median), Month
ALL	490	158	0.1 - 111.0 (35.2)
DEL PEAK 18(13Q13.3) CNV	75	34	0.1 - 89.4 (28.5)
DEL PEAK 18(13Q13.3) WILD-TYPE	415	124	0.1 - 111.0 (36.3)

Figure S15. Get High-res Image Gene #31: 'Del Peak 18(13q13.3)' versus Clinical Feature #1: 'Time to Death'

'Del Peak 18(13q13.3)' versus 'NEOPLASM.DISEASESTAGE'

P value = 0.000129 (Fisher's exact test), Q value = 0.027

Table S16. Gene #31: 'Del Peak 18(13q13.3)' versus Clinical Feature #8: 'NEOPLASM.DISEASESTAGE'

nPatients	STAGE I	STAGE II	STAGE III	STAGE IV
ALL	237	53	126	77
DEL PEAK 18(13Q13.3) CNV	26	2	28	20
DEL PEAK 18(13Q13.3) WILD-TYPE	211	51	98	57

Figure S16. Get High-res Image Gene #31: 'Del Peak 18(13q13.3)' versus Clinical Feature #8: 'NEOPLASM.DISEASESTAGE'

'Del Peak 19(14q31.1)' versus 'DISTANT.METASTASIS'

P value = 0.00101 (Fisher's exact test), Q value = 0.21

Table S17. Gene #32: 'Del Peak 19(14q31.1)' versus Clinical Feature #5: 'DISTANT.METASTASIS'

nPatients	M0	M1
ALL	417	76
DEL PEAK 19(14Q31.1) CNV	171	47
DEL PEAK 19(14Q31.1) WILD-TYPE	246	29

Figure S17. Get High-res Image Gene #32: 'Del Peak 19(14q31.1)' versus Clinical Feature #5: 'DISTANT.METASTASIS'

'Del Peak 19(14q31.1)' versus 'LYMPH.NODE.METASTASIS'

P value = 0.000371 (Fisher's exact test), Q value = 0.078

Table S18. Gene #32: 'Del Peak 19(14q31.1)' versus Clinical Feature #6: 'LYMPH.NODE.METASTASIS'

nPatients	N0	N1	NX
ALL	228	18	247
DEL PEAK 19(14Q31.1) CNV	96	16	106
DEL PEAK 19(14Q31.1) WILD-TYPE	132	2	141

Figure S18. Get High-res Image Gene #32: 'Del Peak 19(14q31.1)' versus Clinical Feature #6: 'LYMPH.NODE.METASTASIS'

'Del Peak 19(14q31.1)' versus 'NEOPLASM.DISEASESTAGE'

P value = 1.48e-05 (Fisher's exact test), Q value = 0.0032

Table S19. Gene #32: 'Del Peak 19(14q31.1)' versus Clinical Feature #8: 'NEOPLASM.DISEASESTAGE'

nPatients	STAGE I	STAGE II	STAGE III	STAGE IV
ALL	237	53	126	77
DEL PEAK 19(14Q31.1) CNV	78	27	67	46
DEL PEAK 19(14Q31.1) WILD-TYPE	159	26	59	31

Figure S19. Get High-res Image Gene #32: 'Del Peak 19(14q31.1)' versus Clinical Feature #8: 'NEOPLASM.DISEASESTAGE'

Methods & Data

Input

Mutation data file = all_lesions.conf_99.cnv.cluster.txt
Clinical data file = KIRC-TP.clin.merged.picked.txt
Number of patients = 493
Number of significantly arm-level cnvs = 32
Number of selected clinical features = 8
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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