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

Adrenocortical Carcinoma (Primary solid tumor)

15 July 2014 | analyses__2014_07_15

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 (2014): Correlation between copy number variation genes (focal events) and selected clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C14J0CT4

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 45 focal events and 7 clinical features across 80 patients, one significant finding detected with Q value < 0.25.

del_4q34.3 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 45 focal events and 7 clinical features. Shown in the table are P values (Q values). Thresholded by Q value < 0.25, one significant finding detected.


		Clinical Features	Time to Death	AGE	NEOPLASM DISEASESTAGE	PATHOLOGY T STAGE	PATHOLOGY N STAGE	GENDER	ETHNICITY
	nCNV (%)	nWild-Type	logrank test	Wilcoxon-test	Fisher's exact test	Fisher's exact test	Fisher's exact test	Fisher's exact test	Fisher's exact test
del 4q34 3	19 (24%)	61	0.000338 (0.107)	0.941 (1.00)	0.0355 (1.00)	0.0598 (1.00)	0.691 (1.00)	1 (1.00)	0.648 (1.00)
amp 1q22	15 (19%)	65	0.00255 (0.799)	0.698 (1.00)	0.737 (1.00)	0.868 (1.00)	0.676 (1.00)	1 (1.00)	0.602 (1.00)
amp 4p16 3	36 (45%)	44	0.229 (1.00)	0.674 (1.00)	0.946 (1.00)	0.927 (1.00)	0.748 (1.00)	0.638 (1.00)	0.402 (1.00)
amp 4q35 1	26 (32%)	54	0.139 (1.00)	0.582 (1.00)	0.237 (1.00)	0.387 (1.00)	0.153 (1.00)	0.453 (1.00)	1 (1.00)
amp 5p15 33	59 (74%)	21	0.59 (1.00)	0.718 (1.00)	0.554 (1.00)	0.554 (1.00)	1 (1.00)	1 (1.00)	0.39 (1.00)
amp 5q35 3	57 (71%)	23	0.135 (1.00)	0.778 (1.00)	0.411 (1.00)	0.705 (1.00)	1 (1.00)	1 (1.00)	0.685 (1.00)
amp 6p21 31	14 (18%)	66	0.5 (1.00)	0.00412 (1.00)	0.718 (1.00)	0.657 (1.00)	1 (1.00)	0.76 (1.00)	0.117 (1.00)
amp 6q24 3	15 (19%)	65	0.928 (1.00)	0.405 (1.00)	0.844 (1.00)	0.735 (1.00)	0.193 (1.00)	0.766 (1.00)	0.568 (1.00)
amp 7p22 1	48 (60%)	32	0.975 (1.00)	0.91 (1.00)	0.12 (1.00)	0.136 (1.00)	0.304 (1.00)	0.812 (1.00)	1 (1.00)
amp 9q31 3	27 (34%)	53	0.000971 (0.305)	0.863 (1.00)	0.0285 (1.00)	0.159 (1.00)	0.0279 (1.00)	0.621 (1.00)	0.221 (1.00)
amp 12q14 1	62 (78%)	18	0.78 (1.00)	0.486 (1.00)	0.932 (1.00)	0.947 (1.00)	0.678 (1.00)	1 (1.00)	0.154 (1.00)
amp 14q11 2	23 (29%)	57	0.514 (1.00)	0.0406 (1.00)	0.294 (1.00)	0.413 (1.00)	0.0277 (1.00)	0.796 (1.00)	0.226 (1.00)
amp 16p13 3	45 (56%)	35	0.457 (1.00)	0.938 (1.00)	0.898 (1.00)	0.953 (1.00)	1 (1.00)	0.348 (1.00)	1 (1.00)
amp 16q22 1	50 (62%)	30	0.574 (1.00)	0.429 (1.00)	0.789 (1.00)	0.737 (1.00)	0.739 (1.00)	0.629 (1.00)	1 (1.00)
amp 16q24 2	44 (55%)	36	0.336 (1.00)	0.877 (1.00)	0.602 (1.00)	0.474 (1.00)	0.742 (1.00)	0.488 (1.00)	0.691 (1.00)
amp 17q25 3	14 (18%)	66	0.5 (1.00)	0.239 (1.00)	0.67 (1.00)	0.473 (1.00)	0.679 (1.00)	1 (1.00)	1 (1.00)
amp 19p13 12	51 (64%)	29	0.354 (1.00)	0.0647 (1.00)	0.171 (1.00)	0.262 (1.00)	0.479 (1.00)	0.808 (1.00)	0.21 (1.00)
amp 19q12	48 (60%)	32	0.192 (1.00)	0.0235 (1.00)	0.158 (1.00)	0.258 (1.00)	0.732 (1.00)	0.637 (1.00)	0.108 (1.00)
amp xp11 22	42 (52%)	38	0.998 (1.00)	0.686 (1.00)	0.876 (1.00)	0.942 (1.00)	0.332 (1.00)	0.245 (1.00)	0.0316 (1.00)
amp xq28	40 (50%)	40	0.23 (1.00)	0.814 (1.00)	0.986 (1.00)	0.968 (1.00)	1 (1.00)	0.815 (1.00)	1 (1.00)
del 1p36 23	35 (44%)	45	0.746 (1.00)	0.47 (1.00)	0.796 (1.00)	0.851 (1.00)	0.742 (1.00)	0.482 (1.00)	1 (1.00)
del 1q43	17 (21%)	63	0.875 (1.00)	0.613 (1.00)	0.597 (1.00)	0.242 (1.00)	0.425 (1.00)	0.576 (1.00)	0.568 (1.00)
del 2q22 1	17 (21%)	63	0.105 (1.00)	0.902 (1.00)	0.356 (1.00)	0.694 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)
del 2q37 3	20 (25%)	60	0.413 (1.00)	0.907 (1.00)	0.141 (1.00)	0.831 (1.00)	1 (1.00)	1 (1.00)	0.568 (1.00)
del 3q13 31	21 (26%)	59	0.0989 (1.00)	0.223 (1.00)	0.227 (1.00)	0.498 (1.00)	1 (1.00)	0.188 (1.00)	0.346 (1.00)
del 4q35 1	23 (29%)	57	0.0275 (1.00)	0.823 (1.00)	0.13 (1.00)	0.132 (1.00)	1 (1.00)	0.438 (1.00)	0.648 (1.00)
del 6p24 3	18 (22%)	62	0.671 (1.00)	0.289 (1.00)	0.399 (1.00)	0.89 (1.00)	1 (1.00)	0.781 (1.00)	1 (1.00)
del 6q26	20 (25%)	60	0.24 (1.00)	0.215 (1.00)	0.0246 (1.00)	0.0397 (1.00)	0.714 (1.00)	0.417 (1.00)	1 (1.00)
del 7q32 3	8 (10%)	72	0.131 (1.00)	0.404 (1.00)	0.701 (1.00)	0.349 (1.00)	1 (1.00)	1 (1.00)	0.553 (1.00)
del 9p23	21 (26%)	59	0.0397 (1.00)	0.857 (1.00)	0.94 (1.00)	0.624 (1.00)	0.439 (1.00)	0.43 (1.00)	0.396 (1.00)
del 9p21 3	24 (30%)	56	0.0261 (1.00)	0.629 (1.00)	1 (1.00)	0.926 (1.00)	0.266 (1.00)	0.801 (1.00)	0.661 (1.00)
del 10q23 1	9 (11%)	71	0.613 (1.00)	0.389 (1.00)	0.317 (1.00)	0.633 (1.00)	0.331 (1.00)	1 (1.00)	1 (1.00)
del 11p15 5	26 (32%)	54	0.502 (1.00)	0.738 (1.00)	0.488 (1.00)	0.981 (1.00)	0.27 (1.00)	0.211 (1.00)	1 (1.00)
del 11q14 1	23 (29%)	57	0.435 (1.00)	0.46 (1.00)	0.124 (1.00)	0.478 (1.00)	0.719 (1.00)	0.195 (1.00)	1 (1.00)
del 12q14 2	5 (6%)	75	0.0444 (1.00)	0.33 (1.00)	0.332 (1.00)	0.546 (1.00)	1 (1.00)	0.653 (1.00)	1 (1.00)
del 13q14 2	36 (45%)	44	0.136 (1.00)	0.558 (1.00)	0.264 (1.00)	0.522 (1.00)	1 (1.00)	0.638 (1.00)	1 (1.00)
del 14q21 2	18 (22%)	62	0.971 (1.00)	0.751 (1.00)	0.458 (1.00)	0.513 (1.00)	0.106 (1.00)	0.404 (1.00)	0.346 (1.00)
del 16p13 3	6 (8%)	74	0.0538 (1.00)	0.499 (1.00)	0.549 (1.00)	0.423 (1.00)	0.579 (1.00)	0.659 (1.00)	0.124 (1.00)
del 16q23 1	6 (8%)	74	0.089 (1.00)	0.596 (1.00)	0.248 (1.00)	0.0838 (1.00)	1 (1.00)	0.176 (1.00)	1 (1.00)
del 17q11 2	23 (29%)	57	0.00474 (1.00)	0.932 (1.00)	0.07 (1.00)	0.0264 (1.00)	1 (1.00)	0.0185 (1.00)	0.648 (1.00)
del 17q21 31	26 (32%)	54	0.144 (1.00)	0.735 (1.00)	0.34 (1.00)	0.183 (1.00)	1 (1.00)	0.0789 (1.00)	0.387 (1.00)
del 17q24 2	24 (30%)	56	0.0147 (1.00)	0.966 (1.00)	0.00462 (1.00)	0.125 (1.00)	0.459 (1.00)	0.078 (1.00)	1 (1.00)
del 18q21 2	34 (42%)	46	0.801 (1.00)	0.37 (1.00)	0.443 (1.00)	0.706 (1.00)	0.509 (1.00)	0.0615 (1.00)	1 (1.00)
del 20p12 1	9 (11%)	71	0.00643 (1.00)	0.365 (1.00)	0.326 (1.00)	0.411 (1.00)	0.587 (1.00)	0.483 (1.00)	0.0471 (1.00)
del 22q12 1	46 (58%)	34	0.0998 (1.00)	0.113 (1.00)	0.212 (1.00)	0.116 (1.00)	0.737 (1.00)	0.236 (1.00)	0.244 (1.00)

'del_4q34.3' versus 'Time to Death'

P value = 0.000338 (logrank test), Q value = 0.11

Table S1. Gene #25: 'del_4q34.3' versus Clinical Feature #1: 'Time to Death'

	nPatients	nDeath	Duration Range (Median), Month
ALL	79	27	4.1 - 153.6 (31.2)
DEL PEAK 6(4Q34.3) MUTATED	18	10	4.9 - 50.7 (18.3)
DEL PEAK 6(4Q34.3) WILD-TYPE	61	17	4.1 - 153.6 (38.9)

Figure S1. Get High-res Image Gene #25: 'del_4q34.3' versus Clinical Feature #1: 'Time to Death'

Methods & Data

Input

Copy number data file = transformed.cor.cli.txt
Clinical data file = ACC-TP.merged_data.txt
Number of patients = 80
Number of significantly focal cnvs = 45
Number of selected clinical features = 7
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

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] 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)

[3] 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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