Correlation between copy number variations of arm-level result and selected clinical features

Acute Myeloid Leukemia (Primary blood derived cancer - Peripheral blood)

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 variations of arm-level result and selected clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C1WW7FQJ

Overview

Introduction

This pipeline computes the correlation between significant arm-level copy number variations (cnvs) and selected clinical features.

Summary

Testing the association between copy number variation 22 arm-level results and 3 clinical features across 191 patients, 4 significant findings detected with Q value < 0.25.

5q loss cnv correlated to 'Time to Death'.
7q loss cnv correlated to 'Time to Death'.
18p loss cnv correlated to 'Time to Death'.
18q loss 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 22 arm-level results and 3 clinical features. Shown in the table are P values (Q values). Thresholded by Q value < 0.25, 4 significant findings detected.


		Clinical Features	Time to Death	AGE	GENDER
	nCNV (%)	nWild-Type	logrank test	t-test	Fisher's exact test
5q loss	0 (0%)	185	0.00073 (0.0438)	0.0601 (1.00)	0.0325 (1.00)
7q loss	0 (0%)	173	0.00315 (0.183)	0.325 (1.00)	0.805 (1.00)
18p loss	0 (0%)	186	0.00202 (0.119)	0.355 (1.00)	0.0642 (1.00)
18q loss	0 (0%)	188	0.000113 (0.00689)	0.0297 (1.00)	0.252 (1.00)
1p gain	0 (0%)	188		0.0913 (1.00)	0.592 (1.00)
4p gain	0 (0%)	187	0.587 (1.00)	0.425 (1.00)	0.627 (1.00)
4q gain	0 (0%)	187	0.587 (1.00)	0.425 (1.00)	0.627 (1.00)
8p gain	0 (0%)	171	0.48 (1.00)	0.119 (1.00)	0.0597 (1.00)
8q gain	0 (0%)	170	0.529 (1.00)	0.168 (1.00)	0.0382 (1.00)
10q gain	0 (0%)	188		0.947 (1.00)	0.252 (1.00)
11p gain	0 (0%)	187		0.188 (1.00)	1 (1.00)
11q gain	0 (0%)	184	0.57 (1.00)	0.0154 (0.834)	1 (1.00)
13q gain	0 (0%)	188		0.511 (1.00)	0.592 (1.00)
17q gain	0 (0%)	188	0.729 (1.00)	0.29 (1.00)	1 (1.00)
19p gain	0 (0%)	186	0.347 (1.00)	0.789 (1.00)	0.0642 (1.00)
19q gain	0 (0%)	186	0.347 (1.00)	0.789 (1.00)	0.0642 (1.00)
21q gain	0 (0%)	183	0.0186 (0.966)	0.616 (1.00)	0.0732 (1.00)
22q gain	0 (0%)	183	0.887 (1.00)	0.00598 (0.341)	0.73 (1.00)
7p loss	0 (0%)	176	0.00716 (0.401)	0.325 (1.00)	1 (1.00)
12p loss	0 (0%)	188		0.514 (1.00)	1 (1.00)
17p loss	0 (0%)	181	0.376 (1.00)	0.308 (1.00)	0.114 (1.00)
17q loss	0 (0%)	186	0.0166 (0.882)	0.0075 (0.412)	0.378 (1.00)

'5q loss' versus 'Time to Death'

P value = 0.00073 (logrank test), Q value = 0.044

Table S1. Gene #15: '5q loss' versus Clinical Feature #1: 'Time to Death'

	nPatients	nDeath	Duration Range (Median), Month
ALL	168	106	0.9 - 94.1 (12.0)
5Q LOSS CNV	6	6	1.0 - 12.0 (7.0)
5Q LOSS WILD-TYPE	162	100	0.9 - 94.1 (12.5)

Figure S1. Get High-res Image Gene #15: '5q loss' versus Clinical Feature #1: 'Time to Death'

'7q loss' versus 'Time to Death'

P value = 0.00315 (logrank test), Q value = 0.18

Table S2. Gene #17: '7q loss' versus Clinical Feature #1: 'Time to Death'

	nPatients	nDeath	Duration Range (Median), Month
ALL	168	106	0.9 - 94.1 (12.0)
7Q LOSS CNV	15	13	1.0 - 40.0 (9.0)
7Q LOSS WILD-TYPE	153	93	0.9 - 94.1 (13.9)

Figure S2. Get High-res Image Gene #17: '7q loss' versus Clinical Feature #1: 'Time to Death'

'18p loss' versus 'Time to Death'

P value = 0.00202 (logrank test), Q value = 0.12

Table S3. Gene #21: '18p loss' versus Clinical Feature #1: 'Time to Death'

	nPatients	nDeath	Duration Range (Median), Month
ALL	168	106	0.9 - 94.1 (12.0)
18P LOSS CNV	5	5	1.0 - 12.0 (7.0)
18P LOSS WILD-TYPE	163	101	0.9 - 94.1 (12.0)

Figure S3. Get High-res Image Gene #21: '18p loss' versus Clinical Feature #1: 'Time to Death'

'18q loss' versus 'Time to Death'

P value = 0.000113 (logrank test), Q value = 0.0069

Table S4. Gene #22: '18q loss' versus Clinical Feature #1: 'Time to Death'

	nPatients	nDeath	Duration Range (Median), Month
ALL	168	106	0.9 - 94.1 (12.0)
18Q LOSS CNV	3	3	1.0 - 7.0 (2.0)
18Q LOSS WILD-TYPE	165	103	0.9 - 94.1 (12.0)

Figure S4. Get High-res Image Gene #22: '18q loss' versus Clinical Feature #1: 'Time to Death'

Methods & Data

Input

Mutation data file = broad_values_by_arm.mutsig.cluster.txt
Clinical data file = LAML-TB.clin.merged.picked.txt
Number of patients = 191
Number of significantly arm-level cnvs = 22
Number of selected clinical features = 3
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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