Correlation between copy number variations of arm-level result and molecular subtypes

Esophageal Carcinoma (Primary solid tumor)

16 April 2014 | analyses__2014_04_16

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 molecular subtypes. Broad Institute of MIT and Harvard. doi:10.7908/C1Q81BNC

Overview

Introduction

This pipeline computes the correlation between significant arm-level copy number variations (cnvs) and molecular subtypes.

Summary

Testing the association between copy number variation 80 arm-level events and 8 molecular subtypes across 103 patients, 5 significant findings detected with P value < 0.05 and Q value < 0.25.

3q gain cnv correlated to 'CN_CNMF'.
12p gain cnv correlated to 'CN_CNMF'.
22q gain cnv correlated to 'METHLYATION_CNMF'.
16q loss cnv correlated to 'CN_CNMF'.
17p loss cnv correlated to 'METHLYATION_CNMF'.

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 molecular subtypes. Shown in the table are P values (Q values). Thresholded by P value < 0.05 and Q value < 0.25, 5 significant findings detected.


		Clinical Features	CN CNMF	METHLYATION CNMF	MRNASEQ CNMF	MRNASEQ CHIERARCHICAL	MIRSEQ CNMF	MIRSEQ CHIERARCHICAL	MIRSEQ MATURE CNMF	MIRSEQ MATURE CHIERARCHICAL
	nCNV (%)	nWild-Type	Fisher's exact 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	Fisher's exact test
3q gain	39 (38%)	64	2.68e-05 (0.0171)	0.0248 (1.00)	0.06 (1.00)	0.00574 (1.00)	0.00218 (1.00)	0.00131 (0.812)	0.0102 (1.00)	0.00131 (0.812)
12p gain	36 (35%)	67	6.56e-05 (0.0418)	0.0686 (1.00)	0.0399 (1.00)	0.00316 (1.00)	0.0123 (1.00)	0.00479 (1.00)	0.0656 (1.00)	0.00479 (1.00)
22q gain	19 (18%)	84	0.00259 (1.00)	0.00011 (0.0698)	0.00115 (0.715)	0.000667 (0.42)	0.00202 (1.00)	0.0011 (0.687)	0.00966 (1.00)	0.0011 (0.687)
16q loss	29 (28%)	74	0.000176 (0.112)	0.0305 (1.00)	0.04 (1.00)	0.0271 (1.00)	0.0621 (1.00)	0.0534 (1.00)	0.133 (1.00)	0.0534 (1.00)
17p loss	37 (36%)	66	0.334 (1.00)	0.000262 (0.166)	0.075 (1.00)	0.0404 (1.00)	0.0526 (1.00)	0.0239 (1.00)	0.0334 (1.00)	0.0239 (1.00)
1p gain	17 (17%)	86	0.0399 (1.00)	0.907 (1.00)	0.308 (1.00)	0.39 (1.00)	0.304 (1.00)	0.301 (1.00)	0.0402 (1.00)	0.301 (1.00)
1q gain	32 (31%)	71	0.0313 (1.00)	0.142 (1.00)	0.0352 (1.00)	0.027 (1.00)	0.0292 (1.00)	0.0103 (1.00)	0.00743 (1.00)	0.0103 (1.00)
2p gain	40 (39%)	63	0.000642 (0.404)	0.328 (1.00)	0.36 (1.00)	0.602 (1.00)	0.116 (1.00)	0.689 (1.00)	0.00928 (1.00)	0.689 (1.00)
2q gain	30 (29%)	73	0.0677 (1.00)	0.0762 (1.00)	0.638 (1.00)	0.551 (1.00)	0.43 (1.00)	0.765 (1.00)	0.0236 (1.00)	0.765 (1.00)
3p gain	14 (14%)	89	0.14 (1.00)	0.779 (1.00)	0.423 (1.00)	0.272 (1.00)	0.101 (1.00)	0.306 (1.00)	0.0533 (1.00)	0.306 (1.00)
4p gain	10 (10%)	93	0.916 (1.00)	0.565 (1.00)	0.84 (1.00)	1 (1.00)	0.735 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)
4q gain	9 (9%)	94	0.563 (1.00)	0.178 (1.00)	0.234 (1.00)	0.576 (1.00)	0.183 (1.00)	0.443 (1.00)	0.531 (1.00)	0.443 (1.00)
5p gain	45 (44%)	58	0.0282 (1.00)	0.222 (1.00)	0.407 (1.00)	0.0874 (1.00)	0.293 (1.00)	0.375 (1.00)	0.36 (1.00)	0.375 (1.00)
5q gain	15 (15%)	88	0.657 (1.00)	0.885 (1.00)	0.75 (1.00)	1 (1.00)	0.749 (1.00)	0.57 (1.00)	1 (1.00)	0.57 (1.00)
6p gain	17 (17%)	86	0.526 (1.00)	1 (1.00)	0.0146 (1.00)	0.625 (1.00)	1 (1.00)	1 (1.00)	0.681 (1.00)	1 (1.00)
6q gain	16 (16%)	87	0.199 (1.00)	0.584 (1.00)	0.00692 (1.00)	0.698 (1.00)	1 (1.00)	1 (1.00)	0.956 (1.00)	1 (1.00)
7p gain	62 (60%)	41	0.0243 (1.00)	0.4 (1.00)	0.00126 (0.786)	0.243 (1.00)	0.667 (1.00)	0.418 (1.00)	0.535 (1.00)	0.418 (1.00)
7q gain	49 (48%)	54	0.358 (1.00)	0.0743 (1.00)	0.437 (1.00)	0.788 (1.00)	0.514 (1.00)	0.399 (1.00)	0.371 (1.00)	0.399 (1.00)
8p gain	39 (38%)	64	0.311 (1.00)	0.436 (1.00)	0.537 (1.00)	1 (1.00)	0.799 (1.00)	1 (1.00)	0.867 (1.00)	1 (1.00)
8q gain	56 (54%)	47	0.153 (1.00)	0.325 (1.00)	0.936 (1.00)	0.403 (1.00)	0.791 (1.00)	0.546 (1.00)	0.769 (1.00)	0.546 (1.00)
9p gain	12 (12%)	91	1 (1.00)	0.667 (1.00)	0.346 (1.00)	0.32 (1.00)	0.697 (1.00)	0.525 (1.00)	0.463 (1.00)	0.525 (1.00)
9q gain	23 (22%)	80	1 (1.00)	0.38 (1.00)	0.395 (1.00)	0.547 (1.00)	0.418 (1.00)	0.5 (1.00)	0.596 (1.00)	0.5 (1.00)
10p gain	21 (20%)	82	0.641 (1.00)	0.161 (1.00)	0.509 (1.00)	0.841 (1.00)	0.0902 (1.00)	0.764 (1.00)	0.217 (1.00)	0.764 (1.00)
10q gain	16 (16%)	87	0.199 (1.00)	0.324 (1.00)	1 (1.00)	0.164 (1.00)	0.221 (1.00)	1 (1.00)	0.331 (1.00)	1 (1.00)
11p gain	20 (19%)	83	0.673 (1.00)	0.772 (1.00)	0.0372 (1.00)	0.593 (1.00)	0.513 (1.00)	0.48 (1.00)	0.518 (1.00)	0.48 (1.00)
11q gain	19 (18%)	84	0.487 (1.00)	0.182 (1.00)	0.106 (1.00)	0.0922 (1.00)	0.206 (1.00)	0.198 (1.00)	0.451 (1.00)	0.198 (1.00)
12q gain	21 (20%)	82	0.00807 (1.00)	0.25 (1.00)	0.505 (1.00)	0.037 (1.00)	0.239 (1.00)	0.336 (1.00)	0.51 (1.00)	0.336 (1.00)
13q gain	24 (23%)	79	0.000399 (0.252)	0.00113 (0.704)	0.00509 (1.00)	0.00346 (1.00)	0.00139 (0.863)	0.000595 (0.376)	0.00204 (1.00)	0.000595 (0.376)
14q gain	26 (25%)	77	0.124 (1.00)	0.113 (1.00)	0.24 (1.00)	0.339 (1.00)	0.469 (1.00)	0.457 (1.00)	0.238 (1.00)	0.457 (1.00)
15q gain	19 (18%)	84	0.706 (1.00)	0.0487 (1.00)	0.476 (1.00)	0.317 (1.00)	0.158 (1.00)	0.426 (1.00)	0.682 (1.00)	0.426 (1.00)
16p gain	20 (19%)	83	0.0279 (1.00)	0.305 (1.00)	0.023 (1.00)	0.0365 (1.00)	0.0971 (1.00)	0.0612 (1.00)	0.0687 (1.00)	0.0612 (1.00)
16q gain	16 (16%)	87	0.0237 (1.00)	0.144 (1.00)	0.00143 (0.887)	0.0563 (1.00)	0.0345 (1.00)	0.0594 (1.00)	0.0133 (1.00)	0.0594 (1.00)
17p gain	19 (18%)	84	0.0169 (1.00)	0.0756 (1.00)	0.45 (1.00)	0.852 (1.00)	0.586 (1.00)	0.679 (1.00)	0.714 (1.00)	0.679 (1.00)
17q gain	24 (23%)	79	0.00441 (1.00)	0.304 (1.00)	0.472 (1.00)	0.411 (1.00)	0.352 (1.00)	0.46 (1.00)	0.749 (1.00)	0.46 (1.00)
18p gain	28 (27%)	75	0.0078 (1.00)	0.301 (1.00)	0.437 (1.00)	0.467 (1.00)	0.447 (1.00)	0.517 (1.00)	0.405 (1.00)	0.517 (1.00)
18q gain	14 (14%)	89	0.562 (1.00)	0.813 (1.00)	0.829 (1.00)	0.625 (1.00)	0.812 (1.00)	0.765 (1.00)	0.956 (1.00)	0.765 (1.00)
19p gain	15 (15%)	88	0.0244 (1.00)	0.399 (1.00)	0.966 (1.00)	0.68 (1.00)	0.763 (1.00)	0.782 (1.00)	0.359 (1.00)	0.782 (1.00)
19q gain	19 (18%)	84	0.00241 (1.00)	0.0957 (1.00)	0.188 (1.00)	0.0834 (1.00)	0.0848 (1.00)	0.0621 (1.00)	0.0446 (1.00)	0.0621 (1.00)
20p gain	53 (51%)	50	0.412 (1.00)	0.184 (1.00)	0.52 (1.00)	0.309 (1.00)	0.54 (1.00)	0.448 (1.00)	0.782 (1.00)	0.448 (1.00)
20q gain	60 (58%)	43	0.0846 (1.00)	0.0221 (1.00)	0.106 (1.00)	0.0708 (1.00)	0.12 (1.00)	0.0516 (1.00)	0.335 (1.00)	0.0516 (1.00)
21q gain	8 (8%)	95	0.591 (1.00)	0.705 (1.00)	0.602 (1.00)	0.0928 (1.00)	0.775 (1.00)	0.726 (1.00)	0.108 (1.00)	0.726 (1.00)
xq gain	21 (20%)	82	0.342 (1.00)	0.233 (1.00)	0.411 (1.00)	0.176 (1.00)	0.445 (1.00)	0.37 (1.00)	0.623 (1.00)	0.37 (1.00)
1p loss	19 (18%)	84	0.06 (1.00)	0.182 (1.00)	0.196 (1.00)	0.171 (1.00)	0.208 (1.00)	0.198 (1.00)	0.593 (1.00)	0.198 (1.00)
1q loss	13 (13%)	90	0.00115 (0.715)	0.0639 (1.00)	0.158 (1.00)	0.115 (1.00)	0.076 (1.00)	0.102 (1.00)	0.476 (1.00)	0.102 (1.00)
2p loss	5 (5%)	98	0.438 (1.00)	0.137 (1.00)			0.796 (1.00)	1 (1.00)	0.864 (1.00)	1 (1.00)
2q loss	11 (11%)	92	0.559 (1.00)	0.00377 (1.00)	0.0169 (1.00)	0.17 (1.00)	0.131 (1.00)	0.194 (1.00)	0.218 (1.00)	0.194 (1.00)
3p loss	53 (51%)	50	0.105 (1.00)	0.0412 (1.00)	0.512 (1.00)	0.0811 (1.00)	0.184 (1.00)	0.04 (1.00)	0.181 (1.00)	0.04 (1.00)
3q loss	15 (15%)	88	0.194 (1.00)	0.895 (1.00)	0.123 (1.00)	0.474 (1.00)	0.535 (1.00)	0.587 (1.00)	0.943 (1.00)	0.587 (1.00)
4p loss	56 (54%)	47	0.00783 (1.00)	0.482 (1.00)	0.143 (1.00)	0.457 (1.00)	0.446 (1.00)	0.164 (1.00)	0.698 (1.00)	0.164 (1.00)
4q loss	49 (48%)	54	0.00528 (1.00)	0.229 (1.00)	0.0562 (1.00)	0.747 (1.00)	0.583 (1.00)	1 (1.00)	0.918 (1.00)	1 (1.00)
5p loss	25 (24%)	78	0.246 (1.00)	0.0376 (1.00)	0.0728 (1.00)	0.00212 (1.00)	0.106 (1.00)	0.117 (1.00)	0.00908 (1.00)	0.117 (1.00)
5q loss	42 (41%)	61	0.525 (1.00)	0.11 (1.00)	0.33 (1.00)	0.539 (1.00)	0.669 (1.00)	0.719 (1.00)	0.294 (1.00)	0.719 (1.00)
6p loss	20 (19%)	83	0.237 (1.00)	0.446 (1.00)	0.172 (1.00)	0.313 (1.00)	0.612 (1.00)	0.5 (1.00)	0.608 (1.00)	0.5 (1.00)
6q loss	18 (17%)	85	0.69 (1.00)	0.76 (1.00)	0.226 (1.00)	0.31 (1.00)	0.504 (1.00)	0.421 (1.00)	0.81 (1.00)	0.421 (1.00)
7p loss	7 (7%)	96	0.792 (1.00)	0.4 (1.00)	0.305 (1.00)	0.0359 (1.00)	0.835 (1.00)	0.667 (1.00)	0.00919 (1.00)	0.667 (1.00)
7q loss	12 (12%)	91	0.0943 (1.00)	0.0161 (1.00)	0.888 (1.00)	0.625 (1.00)	1 (1.00)	1 (1.00)	0.801 (1.00)	1 (1.00)
8p loss	33 (32%)	70	0.795 (1.00)	0.863 (1.00)	0.613 (1.00)	0.901 (1.00)	0.855 (1.00)	0.756 (1.00)	0.816 (1.00)	0.756 (1.00)
8q loss	11 (11%)	92	0.784 (1.00)	0.839 (1.00)	0.641 (1.00)	0.492 (1.00)	0.812 (1.00)	0.765 (1.00)	0.288 (1.00)	0.765 (1.00)
9p loss	54 (52%)	49	0.443 (1.00)	0.386 (1.00)	0.616 (1.00)	0.774 (1.00)	0.625 (1.00)	0.433 (1.00)	0.805 (1.00)	0.433 (1.00)
9q loss	33 (32%)	70	0.325 (1.00)	0.368 (1.00)	0.859 (1.00)	0.558 (1.00)	0.447 (1.00)	0.517 (1.00)	0.165 (1.00)	0.517 (1.00)
10p loss	26 (25%)	77	0.124 (1.00)	0.167 (1.00)	0.703 (1.00)	0.253 (1.00)	0.618 (1.00)	0.575 (1.00)	0.841 (1.00)	0.575 (1.00)
10q loss	31 (30%)	72	0.0052 (1.00)	0.0102 (1.00)	0.352 (1.00)	0.0322 (1.00)	0.0976 (1.00)	0.0438 (1.00)	0.124 (1.00)	0.0438 (1.00)
11p loss	29 (28%)	74	0.454 (1.00)	0.707 (1.00)	0.175 (1.00)	0.475 (1.00)	0.322 (1.00)	0.293 (1.00)	0.418 (1.00)	0.293 (1.00)
11q loss	32 (31%)	71	0.0928 (1.00)	0.775 (1.00)	0.686 (1.00)	0.109 (1.00)	0.222 (1.00)	0.225 (1.00)	0.198 (1.00)	0.225 (1.00)
12p loss	18 (17%)	85	0.289 (1.00)	0.146 (1.00)	0.054 (1.00)	0.009 (1.00)	0.00538 (1.00)	0.00504 (1.00)	0.0769 (1.00)	0.00504 (1.00)
12q loss	17 (17%)	86	0.696 (1.00)	0.227 (1.00)	0.098 (1.00)	0.048 (1.00)	0.0536 (1.00)	0.0301 (1.00)	0.171 (1.00)	0.0301 (1.00)
13q loss	41 (40%)	62	0.00551 (1.00)	0.145 (1.00)	0.127 (1.00)	0.0621 (1.00)	0.0737 (1.00)	0.0213 (1.00)	0.0107 (1.00)	0.0213 (1.00)
14q loss	26 (25%)	77	0.107 (1.00)	0.00511 (1.00)	0.0728 (1.00)	0.108 (1.00)	0.0619 (1.00)	0.117 (1.00)	0.0249 (1.00)	0.117 (1.00)
15q loss	25 (24%)	78	0.302 (1.00)	0.229 (1.00)	0.231 (1.00)	0.286 (1.00)	0.529 (1.00)	0.46 (1.00)	0.655 (1.00)	0.46 (1.00)
16p loss	27 (26%)	76	0.00102 (0.639)	0.0249 (1.00)	0.176 (1.00)	0.0495 (1.00)	0.127 (1.00)	0.117 (1.00)	0.138 (1.00)	0.117 (1.00)
17q loss	10 (10%)	93	0.916 (1.00)	0.565 (1.00)	0.431 (1.00)	0.238 (1.00)	0.264 (1.00)	0.307 (1.00)	0.133 (1.00)	0.307 (1.00)
18p loss	36 (35%)	67	0.135 (1.00)	0.0365 (1.00)	0.383 (1.00)	0.373 (1.00)	0.0717 (1.00)	0.526 (1.00)	0.0893 (1.00)	0.526 (1.00)
18q loss	54 (52%)	49	0.844 (1.00)	0.221 (1.00)	0.494 (1.00)	0.268 (1.00)	0.131 (1.00)	0.3 (1.00)	0.212 (1.00)	0.3 (1.00)
19p loss	33 (32%)	70	0.0203 (1.00)	0.187 (1.00)	0.715 (1.00)	0.835 (1.00)	0.0559 (1.00)	0.577 (1.00)	0.0789 (1.00)	0.577 (1.00)
19q loss	27 (26%)	76	0.0103 (1.00)	0.045 (1.00)	0.739 (1.00)	0.356 (1.00)	0.0514 (1.00)	0.225 (1.00)	0.318 (1.00)	0.225 (1.00)
20p loss	14 (14%)	89	1 (1.00)	0.779 (1.00)	0.823 (1.00)	0.822 (1.00)	0.437 (1.00)	0.737 (1.00)	0.611 (1.00)	0.737 (1.00)
20q loss	5 (5%)	98	1 (1.00)	1 (1.00)	0.842 (1.00)	0.635 (1.00)	0.599 (1.00)	0.576 (1.00)	1 (1.00)	0.576 (1.00)
21q loss	58 (56%)	45	0.612 (1.00)	0.0771 (1.00)	0.0141 (1.00)	0.00693 (1.00)	0.15 (1.00)	0.0524 (1.00)	0.0857 (1.00)	0.0524 (1.00)
22q loss	37 (36%)	66	0.0341 (1.00)	0.00614 (1.00)	0.134 (1.00)	0.214 (1.00)	0.287 (1.00)	0.244 (1.00)	0.375 (1.00)	0.244 (1.00)
xq loss	24 (23%)	79	0.37 (1.00)	0.0727 (1.00)	0.184 (1.00)	0.228 (1.00)	0.334 (1.00)	0.389 (1.00)	0.398 (1.00)	0.389 (1.00)

'3q gain' versus 'CN_CNMF'

P value = 2.68e-05 (Fisher's exact test), Q value = 0.017

Table S1. Gene #6: '3q gain' versus Molecular Subtype #1: 'CN_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	38	39	26
3Q GAIN MUTATED	4	20	15
3Q GAIN WILD-TYPE	34	19	11

Figure S1. Get High-res Image Gene #6: '3q gain' versus Molecular Subtype #1: 'CN_CNMF'

'12p gain' versus 'CN_CNMF'

P value = 6.56e-05 (Fisher's exact test), Q value = 0.042

Table S2. Gene #23: '12p gain' versus Molecular Subtype #1: 'CN_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	38	39	26
12P GAIN MUTATED	4	22	10
12P GAIN WILD-TYPE	34	17	16

Figure S2. Get High-res Image Gene #23: '12p gain' versus Molecular Subtype #1: 'CN_CNMF'

'22q gain' versus 'METHLYATION_CNMF'

P value = 0.00011 (Fisher's exact test), Q value = 0.07

Table S3. Gene #39: '22q gain' versus Molecular Subtype #2: 'METHLYATION_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	40	43	20
22Q GAIN MUTATED	1	16	2
22Q GAIN WILD-TYPE	39	27	18

Figure S3. Get High-res Image Gene #39: '22q gain' versus Molecular Subtype #2: 'METHLYATION_CNMF'

'16q loss' versus 'CN_CNMF'

P value = 0.000176 (Fisher's exact test), Q value = 0.11

Table S4. Gene #69: '16q loss' versus Molecular Subtype #1: 'CN_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	38	39	26
16Q LOSS MUTATED	12	3	14
16Q LOSS WILD-TYPE	26	36	12

Figure S4. Get High-res Image Gene #69: '16q loss' versus Molecular Subtype #1: 'CN_CNMF'

'17p loss' versus 'METHLYATION_CNMF'

P value = 0.000262 (Fisher's exact test), Q value = 0.17

Table S5. Gene #70: '17p loss' versus Molecular Subtype #2: 'METHLYATION_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	40	43	20
17P LOSS MUTATED	24	8	5
17P LOSS WILD-TYPE	16	35	15

Figure S5. Get High-res Image Gene #70: '17p loss' versus Molecular Subtype #2: 'METHLYATION_CNMF'

Methods & Data

Input

Copy number data file = transformed.cor.cli.txt
Molecular subtypes file = ESCA-TP.transferedmergedcluster.txt
Number of patients = 103
Number of significantly arm-level cnvs = 80
Number of molecular subtypes = 8
Exclude genes that fewer than K tumors have mutations, K = 3

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] 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)

[2] 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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