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

Kidney Renal Papillary Cell Carcinoma (Primary solid tumor)

23 September 2013 | analyses__2013_09_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 events) and selected clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C18K77CW

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 34 focal events and 10 clinical features across 129 patients, 7 significant findings detected with Q value < 0.25.

DEL PEAK 11(9P21.3) MUTATION ANALYSIS cnv correlated to 'NEOPLASM.DISEASESTAGE' and 'PATHOLOGY.T.STAGE'.
DEL PEAK 13(11Q24.2) MUTATION ANALYSIS cnv correlated to 'Time to Death'.
DEL PEAK 18(16Q24.1) MUTATION ANALYSIS cnv correlated to 'Time to Death'.
DEL PEAK 22(22Q12.2) MUTATION ANALYSIS cnv correlated to 'PATHOLOGY.T.STAGE'.
DEL PEAK 23(XQ21.31) MUTATION ANALYSIS cnv correlated to 'Time to Death'.
DEL PEAK 24(XQ28) MUTATION ANALYSIS cnv correlated to 'Time to Death'.

Results

Overview of the results

Table 1. Get Full Table Overview of the association between significant copy number variation of 34 focal events and 10 clinical features. Shown in the table are P values (Q values). Thresholded by Q value < 0.25, 7 significant findings detected.


		Clinical Features	Time to Death	AGE	NEOPLASM DISEASESTAGE	PATHOLOGY T STAGE	PATHOLOGY N STAGE	PATHOLOGY M STAGE	GENDER	KARNOFSKY PERFORMANCE SCORE	NUMBERPACKYEARSSMOKED	YEAROFTOBACCOSMOKINGONSET
	nCNV (%)	nWild-Type	logrank test	t-test	Fisher's exact test	Fisher's exact test	Fisher's exact test	Fisher's exact test	Fisher's exact test	t-test	t-test	t-test
DEL PEAK 11(9P21 3) MUTATION ANALYSIS	19 (15%)	110	0.0107 (1.00)	0.278 (1.00)	0.000319 (0.0822)	0.000351 (0.0901)	0.0531 (1.00)	0.00696 (1.00)	0.0133 (1.00)	0.398 (1.00)
DEL PEAK 13(11Q24 2) MUTATION ANALYSIS	14 (11%)	115	0.000726 (0.184)	0.00435 (1.00)	0.0108 (1.00)	0.00619 (1.00)	0.351 (1.00)	0.122 (1.00)	1 (1.00)
DEL PEAK 18(16Q24 1) MUTATION ANALYSIS	6 (5%)	123	1.28e-06 (0.000334)	0.998 (1.00)	0.139 (1.00)	0.164 (1.00)	0.171 (1.00)	0.42 (1.00)	0.0739 (1.00)
DEL PEAK 22(22Q12 2) MUTATION ANALYSIS	32 (25%)	97	0.788 (1.00)	0.602 (1.00)	0.00174 (0.437)	0.000643 (0.164)	0.14 (1.00)	0.107 (1.00)	0.0816 (1.00)	0.445 (1.00)
DEL PEAK 23(XQ21 31) MUTATION ANALYSIS	17 (13%)	112	0.000306 (0.0793)	0.135 (1.00)	0.0612 (1.00)	0.0204 (1.00)	0.104 (1.00)	0.293 (1.00)	0.16 (1.00)	0.398 (1.00)
DEL PEAK 24(XQ28) MUTATION ANALYSIS	16 (12%)	113	0.000505 (0.129)	0.183 (1.00)	0.127 (1.00)	0.141 (1.00)	0.0823 (1.00)	0.815 (1.00)	0.0903 (1.00)	0.458 (1.00)
AMP PEAK 1(2Q32 2) MUTATION ANALYSIS	26 (20%)	103	0.17 (1.00)	0.979 (1.00)	0.0209 (1.00)	0.128 (1.00)	0.145 (1.00)	0.0178 (1.00)	0.355 (1.00)	0.501 (1.00)
AMP PEAK 2(2Q32 2) MUTATION ANALYSIS	26 (20%)	103	0.17 (1.00)	0.979 (1.00)	0.0209 (1.00)	0.128 (1.00)	0.145 (1.00)	0.0178 (1.00)	0.355 (1.00)	0.501 (1.00)
AMP PEAK 3(3P14 1) MUTATION ANALYSIS	36 (28%)	93	0.475 (1.00)	0.608 (1.00)	0.0605 (1.00)	0.0336 (1.00)	1 (1.00)	0.254 (1.00)	0.403 (1.00)	0.13 (1.00)
AMP PEAK 4(3Q22 3) MUTATION ANALYSIS	43 (33%)	86	0.27 (1.00)	0.682 (1.00)	0.323 (1.00)	0.101 (1.00)	0.571 (1.00)	0.339 (1.00)	0.227 (1.00)	0.174 (1.00)
AMP PEAK 5(5Q35 2) MUTATION ANALYSIS	21 (16%)	108	0.528 (1.00)	0.94 (1.00)	0.338 (1.00)	0.291 (1.00)	1 (1.00)	0.345 (1.00)	1 (1.00)	0.397 (1.00)
AMP PEAK 6(6P12 3) MUTATION ANALYSIS	4 (3%)	125	0.531 (1.00)	0.348 (1.00)	0.255 (1.00)	0.157 (1.00)	0.434 (1.00)	0.284 (1.00)	1 (1.00)
AMP PEAK 7(7Q22 1) MUTATION ANALYSIS	74 (57%)	55	0.089 (1.00)	0.88 (1.00)	0.00387 (0.939)	0.0156 (1.00)	0.726 (1.00)	0.276 (1.00)	0.178 (1.00)	0.184 (1.00)
AMP PEAK 8(16P11 2) MUTATION ANALYSIS	69 (53%)	60	0.335 (1.00)	0.321 (1.00)	0.698 (1.00)	0.744 (1.00)	0.722 (1.00)	0.163 (1.00)	0.0215 (1.00)	0.648 (1.00)
AMP PEAK 9(17Q25 2) MUTATION ANALYSIS	90 (70%)	39	0.457 (1.00)	0.122 (1.00)	0.893 (1.00)	0.557 (1.00)	0.883 (1.00)	0.00324 (0.793)	0.0219 (1.00)	0.561 (1.00)
AMP PEAK 10(19P13 2) MUTATION ANALYSIS	14 (11%)	115	0.91 (1.00)	0.0437 (1.00)	0.687 (1.00)	0.113 (1.00)	1 (1.00)	0.875 (1.00)	1 (1.00)	0.136 (1.00)
DEL PEAK 1(1P36 31) MUTATION ANALYSIS	27 (21%)	102	0.186 (1.00)	0.683 (1.00)	0.041 (1.00)	0.0226 (1.00)	0.0288 (1.00)	0.0655 (1.00)	0.487 (1.00)	0.377 (1.00)
DEL PEAK 2(2Q36 3) MUTATION ANALYSIS	6 (5%)	123	0.673 (1.00)	0.343 (1.00)	0.0192 (1.00)	0.00266 (0.658)	1 (1.00)	0.0445 (1.00)	0.373 (1.00)
DEL PEAK 3(3P22 1) MUTATION ANALYSIS	10 (8%)	119	0.239 (1.00)	0.086 (1.00)	0.00339 (0.826)	0.00295 (0.726)	0.523 (1.00)	0.103 (1.00)	1 (1.00)
DEL PEAK 4(4Q32 1) MUTATION ANALYSIS	16 (12%)	113	0.115 (1.00)	0.414 (1.00)	0.0612 (1.00)	0.0617 (1.00)	0.0816 (1.00)	0.0439 (1.00)	0.257 (1.00)
DEL PEAK 5(5P14 2) MUTATION ANALYSIS	7 (5%)	122	0.0846 (1.00)	0.151 (1.00)	0.0317 (1.00)	0.00159 (0.4)	0.00816 (1.00)	0.42 (1.00)	0.202 (1.00)
DEL PEAK 6(5Q15) MUTATION ANALYSIS	8 (6%)	121	0.554 (1.00)	0.0553 (1.00)	0.14 (1.00)	0.0237 (1.00)	0.102 (1.00)	0.3 (1.00)	0.253 (1.00)
DEL PEAK 7(5Q35 2) MUTATION ANALYSIS	8 (6%)	121	0.635 (1.00)	0.115 (1.00)	0.0474 (1.00)	0.0116 (1.00)	0.102 (1.00)	0.387 (1.00)	0.253 (1.00)
DEL PEAK 8(6P12 3) MUTATION ANALYSIS	12 (9%)	117	0.381 (1.00)	0.573 (1.00)	0.0263 (1.00)	0.0253 (1.00)	0.178 (1.00)	0.431 (1.00)	1 (1.00)	0.248 (1.00)
DEL PEAK 9(6Q22 31) MUTATION ANALYSIS	13 (10%)	116	0.0643 (1.00)	0.769 (1.00)	0.0713 (1.00)	0.0073 (1.00)	0.525 (1.00)	0.236 (1.00)	0.109 (1.00)	0.383 (1.00)
DEL PEAK 10(6Q25 3) MUTATION ANALYSIS	14 (11%)	115	0.349 (1.00)	0.677 (1.00)	0.021 (1.00)	0.00265 (0.657)	0.839 (1.00)	0.492 (1.00)	0.0338 (1.00)	0.383 (1.00)
DEL PEAK 12(11Q22 3) MUTATION ANALYSIS	14 (11%)	115	0.00193 (0.482)	0.0123 (1.00)	0.0108 (1.00)	0.00619 (1.00)	0.285 (1.00)	0.122 (1.00)	0.762 (1.00)
DEL PEAK 14(14Q11 2) MUTATION ANALYSIS	29 (22%)	100	0.349 (1.00)	0.81 (1.00)	0.11 (1.00)	0.112 (1.00)	0.535 (1.00)	0.24 (1.00)	0.37 (1.00)	0.445 (1.00)
DEL PEAK 15(14Q32 2) MUTATION ANALYSIS	28 (22%)	101	0.288 (1.00)	0.472 (1.00)	0.111 (1.00)	0.16 (1.00)	0.145 (1.00)	0.163 (1.00)	0.645 (1.00)	0.377 (1.00)
DEL PEAK 16(14Q32 2) MUTATION ANALYSIS	28 (22%)	101	0.288 (1.00)	0.507 (1.00)	0.0808 (1.00)	0.0705 (1.00)	0.145 (1.00)	0.23 (1.00)	0.356 (1.00)	0.377 (1.00)
DEL PEAK 17(15Q15 1) MUTATION ANALYSIS	17 (13%)	112	0.00714 (1.00)	0.0732 (1.00)	0.0228 (1.00)	0.00692 (1.00)	0.0062 (1.00)	0.04 (1.00)	0.779 (1.00)	0.354 (1.00)
DEL PEAK 19(19P13 3) MUTATION ANALYSIS	13 (10%)	116	0.148 (1.00)	0.512 (1.00)	0.0387 (1.00)	0.0172 (1.00)	0.789 (1.00)	0.156 (1.00)	1 (1.00)	0.397 (1.00)
DEL PEAK 20(19Q13 2) MUTATION ANALYSIS	11 (9%)	118	0.275 (1.00)	0.368 (1.00)	0.00262 (0.653)	0.00105 (0.265)	1 (1.00)	0.481 (1.00)	1 (1.00)
DEL PEAK 21(19Q13 42) MUTATION ANALYSIS	12 (9%)	117	0.397 (1.00)	0.755 (1.00)	0.26 (1.00)	0.157 (1.00)	1 (1.00)	0.236 (1.00)	0.753 (1.00)

'DEL PEAK 11(9P21.3) MUTATION STATUS' versus 'NEOPLASM.DISEASESTAGE'

P value = 0.000319 (Fisher's exact test), Q value = 0.082

Table S1. Gene #21: 'DEL PEAK 11(9P21.3) MUTATION STATUS' versus Clinical Feature #3: 'NEOPLASM.DISEASESTAGE'

nPatients	STAGE I	STAGE II	STAGE III	STAGE IV
ALL	69	10	30	10
DEL PEAK 11(9P21.3) MUTATED	4	0	8	5
DEL PEAK 11(9P21.3) WILD-TYPE	65	10	22	5

Figure S1. Get High-res Image Gene #21: 'DEL PEAK 11(9P21.3) MUTATION STATUS' versus Clinical Feature #3: 'NEOPLASM.DISEASESTAGE'

'DEL PEAK 11(9P21.3) MUTATION STATUS' versus 'PATHOLOGY.T.STAGE'

P value = 0.000351 (Fisher's exact test), Q value = 0.09

Table S2. Gene #21: 'DEL PEAK 11(9P21.3) MUTATION STATUS' versus Clinical Feature #4: 'PATHOLOGY.T.STAGE'

nPatients	T1	T2	T3+T4
ALL	74	16	39
DEL PEAK 11(9P21.3) MUTATED	4	2	13
DEL PEAK 11(9P21.3) WILD-TYPE	70	14	26

Figure S2. Get High-res Image Gene #21: 'DEL PEAK 11(9P21.3) MUTATION STATUS' versus Clinical Feature #4: 'PATHOLOGY.T.STAGE'

'DEL PEAK 13(11Q24.2) MUTATION STATUS' versus 'Time to Death'

P value = 0.000726 (logrank test), Q value = 0.18

Table S3. Gene #23: 'DEL PEAK 13(11Q24.2) MUTATION STATUS' versus Clinical Feature #1: 'Time to Death'

	nPatients	nDeath	Duration Range (Median), Month
ALL	119	15	0.0 - 194.8 (13.7)
DEL PEAK 13(11Q24.2) MUTATED	13	5	2.0 - 123.6 (11.0)
DEL PEAK 13(11Q24.2) WILD-TYPE	106	10	0.0 - 194.8 (14.4)

Figure S3. Get High-res Image Gene #23: 'DEL PEAK 13(11Q24.2) MUTATION STATUS' versus Clinical Feature #1: 'Time to Death'

'DEL PEAK 18(16Q24.1) MUTATION STATUS' versus 'Time to Death'

P value = 1.28e-06 (logrank test), Q value = 0.00033

Table S4. Gene #28: 'DEL PEAK 18(16Q24.1) MUTATION STATUS' versus Clinical Feature #1: 'Time to Death'

	nPatients	nDeath	Duration Range (Median), Month
ALL	119	15	0.0 - 194.8 (13.7)
DEL PEAK 18(16Q24.1) MUTATED	5	3	0.7 - 21.6 (11.1)
DEL PEAK 18(16Q24.1) WILD-TYPE	114	12	0.0 - 194.8 (13.9)

Figure S4. Get High-res Image Gene #28: 'DEL PEAK 18(16Q24.1) MUTATION STATUS' versus Clinical Feature #1: 'Time to Death'

'DEL PEAK 22(22Q12.2) MUTATION STATUS' versus 'PATHOLOGY.T.STAGE'

P value = 0.000643 (Fisher's exact test), Q value = 0.16

Table S5. Gene #32: 'DEL PEAK 22(22Q12.2) MUTATION STATUS' versus Clinical Feature #4: 'PATHOLOGY.T.STAGE'

nPatients	T1	T2	T3+T4
ALL	74	16	39
DEL PEAK 22(22Q12.2) MUTATED	10	4	18
DEL PEAK 22(22Q12.2) WILD-TYPE	64	12	21

Figure S5. Get High-res Image Gene #32: 'DEL PEAK 22(22Q12.2) MUTATION STATUS' versus Clinical Feature #4: 'PATHOLOGY.T.STAGE'

'DEL PEAK 23(XQ21.31) MUTATION STATUS' versus 'Time to Death'

P value = 0.000306 (logrank test), Q value = 0.079

Table S6. Gene #33: 'DEL PEAK 23(XQ21.31) MUTATION STATUS' versus Clinical Feature #1: 'Time to Death'

	nPatients	nDeath	Duration Range (Median), Month
ALL	119	15	0.0 - 194.8 (13.7)
DEL PEAK 23(XQ21.31) MUTATED	16	5	0.0 - 79.8 (9.9)
DEL PEAK 23(XQ21.31) WILD-TYPE	103	10	0.0 - 194.8 (14.6)

Figure S6. Get High-res Image Gene #33: 'DEL PEAK 23(XQ21.31) MUTATION STATUS' versus Clinical Feature #1: 'Time to Death'

'DEL PEAK 24(XQ28) MUTATION STATUS' versus 'Time to Death'

P value = 0.000505 (logrank test), Q value = 0.13

Table S7. Gene #34: 'DEL PEAK 24(XQ28) MUTATION STATUS' versus Clinical Feature #1: 'Time to Death'

	nPatients	nDeath	Duration Range (Median), Month
ALL	119	15	0.0 - 194.8 (13.7)
DEL PEAK 24(XQ28) MUTATED	15	4	0.0 - 25.1 (10.1)
DEL PEAK 24(XQ28) WILD-TYPE	104	11	0.0 - 194.8 (14.4)

Figure S7. Get High-res Image Gene #34: 'DEL PEAK 24(XQ28) MUTATION STATUS' versus Clinical Feature #1: 'Time to Death'

Methods & Data

Input

Copy number data file = transformed.cor.cli.txt
Clinical data file = KIRP-TP.clin.merged.picked.txt
Number of patients = 129
Number of significantly focal cnvs = 34
Number of selected clinical features = 10
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

In addition to the links below, the full results of the analysis summarized in this report can also be downloaded programmatically using firehose_get, or interactively from either the Broad GDAC website or TCGA Data Coordination Center Portal.

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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