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

Adrenocortical Carcinoma (Primary solid tumor)

17 October 2014 | analyses__2014_10_17

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 variations of arm-level result and selected clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C1N58K6F

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 80 arm-level events and 8 clinical features across 90 patients, 3 significant findings detected with Q value < 0.25.

11q gain cnv correlated to 'Time to Death'.
4p loss cnv correlated to 'Time to Death'.
4q 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 80 arm-level events and 8 clinical features. Shown in the table are P values (Q values). Thresholded by Q value < 0.25, 3 significant findings detected.


		Clinical Features	Time to Death	AGE	NEOPLASM DISEASESTAGE	PATHOLOGY T STAGE	PATHOLOGY N STAGE	GENDER	RACE	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	Fisher's exact test
11q gain	6 (7%)	84	2.09e-05 (0.0134)	0.698 (1.00)	0.121 (1.00)	0.0627 (1.00)	1 (1.00)	0.66 (1.00)	1 (1.00)	1 (1.00)
4p loss	10 (11%)	80	9.39e-05 (0.0599)	0.542 (1.00)	0.018 (1.00)	0.00341 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)
4q loss	11 (12%)	79	1.17e-05 (0.00748)	0.805 (1.00)	0.0233 (1.00)	0.00634 (1.00)	1 (1.00)	0.742 (1.00)	1 (1.00)	1 (1.00)
1p gain	4 (4%)	86	0.095 (1.00)	0.487 (1.00)	1 (1.00)	0.744 (1.00)	1 (1.00)	0.294 (1.00)	0.146 (1.00)	1 (1.00)
1q gain	8 (9%)	82	0.0324 (1.00)	0.798 (1.00)	0.734 (1.00)	0.453 (1.00)	0.589 (1.00)	0.047 (1.00)	0.246 (1.00)	0.557 (1.00)
2p gain	13 (14%)	77	0.000969 (0.615)	0.818 (1.00)	0.377 (1.00)	0.143 (1.00)	0.347 (1.00)	0.205 (1.00)	0.17 (1.00)	0.59 (1.00)
2q gain	12 (13%)	78	0.0316 (1.00)	0.767 (1.00)	0.155 (1.00)	0.239 (1.00)	1 (1.00)	0.0516 (1.00)	0.17 (1.00)	0.651 (1.00)
3p gain	13 (14%)	77	0.292 (1.00)	0.323 (1.00)	0.586 (1.00)	0.929 (1.00)	1 (1.00)	0.759 (1.00)	1 (1.00)	1 (1.00)
3q gain	15 (17%)	75	0.409 (1.00)	0.423 (1.00)	0.334 (1.00)	0.758 (1.00)	0.677 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)
4p gain	37 (41%)	53	0.233 (1.00)	0.941 (1.00)	0.792 (1.00)	0.842 (1.00)	1 (1.00)	0.654 (1.00)	1 (1.00)	0.41 (1.00)
4q gain	33 (37%)	57	0.118 (1.00)	0.97 (1.00)	0.961 (1.00)	0.93 (1.00)	1 (1.00)	0.495 (1.00)	1 (1.00)	0.661 (1.00)
5p gain	57 (63%)	33	0.353 (1.00)	0.854 (1.00)	0.692 (1.00)	0.893 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)	0.132 (1.00)
5q gain	53 (59%)	37	0.633 (1.00)	0.62 (1.00)	0.567 (1.00)	0.796 (1.00)	1 (1.00)	1 (1.00)	0.18 (1.00)	0.113 (1.00)
6p gain	18 (20%)	72	0.531 (1.00)	0.0275 (1.00)	0.5 (1.00)	0.253 (1.00)	0.679 (1.00)	0.588 (1.00)	0.0911 (1.00)	0.0593 (1.00)
6q gain	16 (18%)	74	0.912 (1.00)	0.2 (1.00)	0.115 (1.00)	0.174 (1.00)	0.2 (1.00)	0.399 (1.00)	0.0578 (1.00)	0.618 (1.00)
7p gain	48 (53%)	42	0.891 (1.00)	0.51 (1.00)	0.167 (1.00)	0.23 (1.00)	0.336 (1.00)	1 (1.00)	0.217 (1.00)	0.269 (1.00)
7q gain	48 (53%)	42	0.535 (1.00)	0.859 (1.00)	0.107 (1.00)	0.223 (1.00)	0.336 (1.00)	1 (1.00)	0.215 (1.00)	0.113 (1.00)
8p gain	32 (36%)	58	0.304 (1.00)	0.508 (1.00)	0.443 (1.00)	0.638 (1.00)	0.484 (1.00)	1 (1.00)	0.289 (1.00)	0.41 (1.00)
8q gain	38 (42%)	52	0.913 (1.00)	0.49 (1.00)	0.344 (1.00)	0.535 (1.00)	0.51 (1.00)	1 (1.00)	0.342 (1.00)	0.694 (1.00)
9p gain	20 (22%)	70	0.206 (1.00)	0.716 (1.00)	0.0598 (1.00)	0.327 (1.00)	0.00792 (1.00)	0.791 (1.00)	1 (1.00)	0.382 (1.00)
9q gain	29 (32%)	61	0.0276 (1.00)	0.663 (1.00)	0.0384 (1.00)	0.0895 (1.00)	0.013 (1.00)	0.477 (1.00)	1 (1.00)	0.427 (1.00)
10p gain	25 (28%)	65	0.0161 (1.00)	0.397 (1.00)	0.00608 (1.00)	0.0162 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)	0.427 (1.00)
10q gain	26 (29%)	64	0.00745 (1.00)	0.266 (1.00)	0.00152 (0.964)	0.00562 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)	0.427 (1.00)
11p gain	5 (6%)	85	0.00455 (1.00)	0.364 (1.00)	0.158 (1.00)	0.042 (1.00)	1 (1.00)	0.656 (1.00)	1 (1.00)	0.568 (1.00)
12p gain	64 (71%)	26	0.985 (1.00)	0.287 (1.00)	0.703 (1.00)	0.61 (1.00)	1 (1.00)	0.464 (1.00)	0.65 (1.00)	0.0868 (1.00)
12q gain	64 (71%)	26	0.971 (1.00)	0.415 (1.00)	0.701 (1.00)	0.651 (1.00)	0.718 (1.00)	0.464 (1.00)	0.0825 (1.00)	0.0868 (1.00)
13q gain	6 (7%)	84	0.946 (1.00)	0.651 (1.00)	0.732 (1.00)	0.72 (1.00)	0.526 (1.00)	1 (1.00)	1 (1.00)	0.557 (1.00)
14q gain	21 (23%)	69	0.161 (1.00)	0.426 (1.00)	0.181 (1.00)	0.313 (1.00)	0.241 (1.00)	0.606 (1.00)	1 (1.00)	0.382 (1.00)
15q gain	11 (12%)	79	0.95 (1.00)	0.46 (1.00)	0.796 (1.00)	0.715 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)
16p gain	49 (54%)	41	0.362 (1.00)	0.576 (1.00)	0.592 (1.00)	0.289 (1.00)	1 (1.00)	0.187 (1.00)	0.726 (1.00)	0.443 (1.00)
16q gain	47 (52%)	43	0.19 (1.00)	0.929 (1.00)	0.833 (1.00)	0.613 (1.00)	1 (1.00)	0.269 (1.00)	0.114 (1.00)	0.699 (1.00)
17p gain	5 (6%)	85	0.956 (1.00)	0.622 (1.00)	0.159 (1.00)	0.11 (1.00)	1 (1.00)	1 (1.00)	0.145 (1.00)	0.452 (1.00)
17q gain	7 (8%)	83	0.442 (1.00)	0.488 (1.00)	0.691 (1.00)	0.469 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)	0.557 (1.00)
18p gain	6 (7%)	84	0.137 (1.00)	0.452 (1.00)	0.343 (1.00)	0.33 (1.00)	1 (1.00)	1 (1.00)	0.214 (1.00)	1 (1.00)
18q gain	5 (6%)	85	0.327 (1.00)	0.833 (1.00)	0.831 (1.00)	0.286 (1.00)	1 (1.00)	0.656 (1.00)	0.181 (1.00)	0.568 (1.00)
19p gain	56 (62%)	34	0.422 (1.00)	0.119 (1.00)	0.178 (1.00)	0.202 (1.00)	0.737 (1.00)	0.821 (1.00)	1 (1.00)	0.132 (1.00)
19q gain	52 (58%)	38	0.46 (1.00)	0.0203 (1.00)	0.2 (1.00)	0.328 (1.00)	0.182 (1.00)	0.378 (1.00)	1 (1.00)	0.132 (1.00)
20p gain	46 (51%)	44	0.12 (1.00)	0.495 (1.00)	0.339 (1.00)	0.796 (1.00)	1 (1.00)	0.188 (1.00)	0.492 (1.00)	1 (1.00)
20q gain	49 (54%)	41	0.533 (1.00)	0.964 (1.00)	0.317 (1.00)	0.858 (1.00)	0.336 (1.00)	0.187 (1.00)	0.215 (1.00)	0.705 (1.00)
21q gain	31 (34%)	59	0.706 (1.00)	0.154 (1.00)	0.936 (1.00)	0.94 (1.00)	0.0836 (1.00)	0.818 (1.00)	0.273 (1.00)	0.452 (1.00)
22q gain	3 (3%)	87	0.117 (1.00)	0.208 (1.00)	1 (1.00)	1 (1.00)	0.307 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)
xq gain	40 (44%)	50	0.538 (1.00)	0.929 (1.00)	0.656 (1.00)	0.973 (1.00)	0.336 (1.00)	0.658 (1.00)	0.33 (1.00)	0.252 (1.00)
1p loss	29 (32%)	61	0.994 (1.00)	0.866 (1.00)	0.957 (1.00)	0.951 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)
1q loss	20 (22%)	70	0.744 (1.00)	0.317 (1.00)	0.563 (1.00)	0.746 (1.00)	0.445 (1.00)	0.599 (1.00)	1 (1.00)	1 (1.00)
2p loss	17 (19%)	73	0.0408 (1.00)	0.442 (1.00)	1 (1.00)	0.722 (1.00)	1 (1.00)	0.576 (1.00)	1 (1.00)	1 (1.00)
2q loss	15 (17%)	75	0.0743 (1.00)	0.689 (1.00)	0.617 (1.00)	0.759 (1.00)	1 (1.00)	0.767 (1.00)	1 (1.00)	1 (1.00)
3p loss	20 (22%)	70	0.0773 (1.00)	0.614 (1.00)	0.0922 (1.00)	0.344 (1.00)	1 (1.00)	0.293 (1.00)	1 (1.00)	1 (1.00)
3q loss	20 (22%)	70	0.134 (1.00)	0.907 (1.00)	0.177 (1.00)	0.562 (1.00)	1 (1.00)	0.599 (1.00)	0.251 (1.00)	0.286 (1.00)
5p loss	8 (9%)	82	0.129 (1.00)	0.676 (1.00)	0.187 (1.00)	0.148 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)	0.557 (1.00)
5q loss	7 (8%)	83	0.55 (1.00)	0.342 (1.00)	0.0749 (1.00)	0.144 (1.00)	0.584 (1.00)	0.228 (1.00)	1 (1.00)	1 (1.00)
6p loss	19 (21%)	71	0.0914 (1.00)	0.35 (1.00)	0.0833 (1.00)	0.148 (1.00)	0.445 (1.00)	1 (1.00)	1 (1.00)	0.572 (1.00)
6q loss	22 (24%)	68	0.0616 (1.00)	0.254 (1.00)	0.00668 (1.00)	0.0181 (1.00)	0.706 (1.00)	0.453 (1.00)	1 (1.00)	1 (1.00)
7p loss	5 (6%)	85	0.0757 (1.00)	0.718 (1.00)	0.335 (1.00)	0.286 (1.00)	1 (1.00)	0.0461 (1.00)	1 (1.00)	1 (1.00)
7q loss	6 (7%)	84	0.012 (1.00)	0.61 (1.00)	0.0374 (1.00)	0.0191 (1.00)	1 (1.00)	0.411 (1.00)	1 (1.00)	1 (1.00)
8p loss	16 (18%)	74	0.69 (1.00)	0.768 (1.00)	0.672 (1.00)	0.97 (1.00)	0.365 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)
8q loss	12 (13%)	78	0.968 (1.00)	0.639 (1.00)	0.579 (1.00)	1 (1.00)	0.107 (1.00)	0.534 (1.00)	1 (1.00)	1 (1.00)
9p loss	20 (22%)	70	0.135 (1.00)	0.506 (1.00)	0.846 (1.00)	0.62 (1.00)	0.683 (1.00)	0.599 (1.00)	1 (1.00)	0.651 (1.00)
9q loss	11 (12%)	79	0.874 (1.00)	0.427 (1.00)	0.214 (1.00)	0.426 (1.00)	0.596 (1.00)	1 (1.00)	1 (1.00)	0.568 (1.00)
10p loss	12 (13%)	78	0.359 (1.00)	0.934 (1.00)	0.183 (1.00)	1 (1.00)	0.134 (1.00)	1 (1.00)	1 (1.00)	0.452 (1.00)
10q loss	10 (11%)	80	0.417 (1.00)	0.298 (1.00)	0.308 (1.00)	0.712 (1.00)	0.317 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)
11p loss	24 (27%)	66	0.587 (1.00)	0.722 (1.00)	0.132 (1.00)	0.601 (1.00)	0.706 (1.00)	0.455 (1.00)	1 (1.00)	1 (1.00)
11q loss	23 (26%)	67	0.208 (1.00)	0.563 (1.00)	0.0269 (1.00)	0.164 (1.00)	1 (1.00)	0.317 (1.00)	1 (1.00)	0.568 (1.00)
12p loss	5 (6%)	85	0.188 (1.00)	0.241 (1.00)	0.33 (1.00)	0.284 (1.00)	1 (1.00)	0.335 (1.00)	1 (1.00)	1 (1.00)
12q loss	4 (4%)	86	0.0631 (1.00)	0.463 (1.00)	0.332 (1.00)	0.285 (1.00)	1 (1.00)	0.606 (1.00)	1 (1.00)	1 (1.00)
13q loss	39 (43%)	51	0.144 (1.00)	0.536 (1.00)	0.484 (1.00)	0.92 (1.00)	0.51 (1.00)	0.51 (1.00)	0.505 (1.00)	0.699 (1.00)
14q loss	18 (20%)	72	0.682 (1.00)	0.793 (1.00)	0.835 (1.00)	0.782 (1.00)	0.68 (1.00)	0.782 (1.00)	0.217 (1.00)	0.137 (1.00)
15q loss	21 (23%)	69	0.905 (1.00)	0.519 (1.00)	0.648 (1.00)	0.704 (1.00)	1 (1.00)	0.606 (1.00)	1 (1.00)	0.661 (1.00)
16p loss	6 (7%)	84	0.000668 (0.425)	0.418 (1.00)	0.117 (1.00)	0.0515 (1.00)	0.526 (1.00)	1 (1.00)	1 (1.00)	0.452 (1.00)
16q loss	5 (6%)	85	0.0189 (1.00)	0.214 (1.00)	0.246 (1.00)	0.138 (1.00)	0.461 (1.00)	1 (1.00)	1 (1.00)	0.452 (1.00)
17p loss	32 (36%)	58	0.000652 (0.415)	0.535 (1.00)	0.0603 (1.00)	0.139 (1.00)	0.73 (1.00)	0.246 (1.00)	0.699 (1.00)	0.405 (1.00)
17q loss	24 (27%)	66	0.0112 (1.00)	0.964 (1.00)	0.191 (1.00)	0.361 (1.00)	0.706 (1.00)	0.00587 (1.00)	1 (1.00)	0.661 (1.00)
18p loss	37 (41%)	53	0.708 (1.00)	0.892 (1.00)	0.205 (1.00)	0.496 (1.00)	1 (1.00)	0.37 (1.00)	0.292 (1.00)	1 (1.00)
18q loss	35 (39%)	55	0.883 (1.00)	0.747 (1.00)	0.273 (1.00)	0.518 (1.00)	1 (1.00)	0.11 (1.00)	0.274 (1.00)	1 (1.00)
19p loss	5 (6%)	85	0.00303 (1.00)	0.603 (1.00)	0.194 (1.00)	0.287 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)
19q loss	4 (4%)	86	0.0792 (1.00)	0.124 (1.00)	0.876 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)
20p loss	9 (10%)	81	0.778 (1.00)	0.595 (1.00)	0.555 (1.00)	0.749 (1.00)	1 (1.00)	0.156 (1.00)	0.278 (1.00)	0.557 (1.00)
20q loss	3 (3%)	87	0.386 (1.00)	0.582 (1.00)	0.706 (1.00)	0.522 (1.00)	1 (1.00)	0.549 (1.00)	1 (1.00)	0.327 (1.00)
21q loss	15 (17%)	75	0.0197 (1.00)	0.468 (1.00)	0.67 (1.00)	0.417 (1.00)	1 (1.00)	0.565 (1.00)	1 (1.00)	0.557 (1.00)
22q loss	48 (53%)	42	0.00777 (1.00)	0.236 (1.00)	0.187 (1.00)	0.0827 (1.00)	1 (1.00)	0.374 (1.00)	1 (1.00)	0.113 (1.00)
xq loss	17 (19%)	73	0.891 (1.00)	0.0417 (1.00)	0.976 (1.00)	0.738 (1.00)	0.38 (1.00)	1 (1.00)	1 (1.00)	0.321 (1.00)

'11q gain' versus 'Time to Death'

P value = 2.09e-05 (logrank test), Q value = 0.013

Table S1. Gene #22: '11q gain' versus Clinical Feature #1: 'Time to Death'

	nPatients	nDeath	Duration Range (Median), Month
ALL	89	31	4.1 - 153.6 (36.3)
11Q GAIN MUTATED	6	6	8.3 - 60.9 (15.2)
11Q GAIN WILD-TYPE	83	25	4.1 - 153.6 (36.3)

Figure S1. Get High-res Image Gene #22: '11q gain' versus Clinical Feature #1: 'Time to Death'

'4p loss' versus 'Time to Death'

P value = 9.39e-05 (logrank test), Q value = 0.06

Table S2. Gene #47: '4p loss' versus Clinical Feature #1: 'Time to Death'

	nPatients	nDeath	Duration Range (Median), Month
ALL	89	31	4.1 - 153.6 (36.3)
4P LOSS MUTATED	10	7	4.1 - 46.5 (18.1)
4P LOSS WILD-TYPE	79	24	4.9 - 153.6 (39.6)

Figure S2. Get High-res Image Gene #47: '4p loss' versus Clinical Feature #1: 'Time to Death'

'4q loss' versus 'Time to Death'

P value = 1.17e-05 (logrank test), Q value = 0.0075

Table S3. Gene #48: '4q loss' versus Clinical Feature #1: 'Time to Death'

	nPatients	nDeath	Duration Range (Median), Month
ALL	89	31	4.1 - 153.6 (36.3)
4Q LOSS MUTATED	11	8	4.1 - 46.5 (18.1)
4Q LOSS WILD-TYPE	78	23	4.9 - 153.6 (40.5)

Figure S3. Get High-res Image Gene #48: '4q loss' 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 = 90
Number of significantly arm-level cnvs = 80
Number of selected clinical features = 8
Exclude regions 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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