Correlation between copy number variation genes (focal events) and molecular subtypes

Uterine Carcinosarcoma (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 molecular subtypes. Broad Institute of MIT and Harvard. doi:10.7908/C1VT1QX8

Overview

Introduction

This pipeline computes the correlation between significant copy number variation (cnv focal) genes and molecular subtypes.

Summary

Testing the association between copy number variation 62 focal events and 8 molecular subtypes across 56 patients, 2 significant findings detected with P value < 0.05 and Q value < 0.25.

amp_19q12 cnv correlated to 'METHLYATION_CNMF'.
del_13q14.2 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 62 focal 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, 2 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
amp 19q12	45 (80%)	11	0.00058 (0.287)	8e-05 (0.0397)	0.196 (1.00)	0.0196 (1.00)	0.645 (1.00)	0.5 (1.00)	0.44 (1.00)	0.582 (1.00)
del 13q14 2	32 (57%)	24	0.599 (1.00)	0.00045 (0.223)	0.0133 (1.00)	0.0209 (1.00)	0.479 (1.00)	0.156 (1.00)	0.14 (1.00)	0.304 (1.00)
amp 1q22	42 (75%)	14	0.922 (1.00)	0.225 (1.00)	0.476 (1.00)	0.296 (1.00)	0.183 (1.00)	0.187 (1.00)	0.241 (1.00)	0.49 (1.00)
amp 2p14	28 (50%)	28	0.499 (1.00)	0.0262 (1.00)	0.00696 (1.00)	0.0799 (1.00)	0.488 (1.00)	0.247 (1.00)	0.382 (1.00)	0.0839 (1.00)
amp 2q13	29 (52%)	27	0.386 (1.00)	0.0162 (1.00)	0.0465 (1.00)	0.319 (1.00)	1 (1.00)	0.664 (1.00)	0.841 (1.00)	0.336 (1.00)
amp 3p25 1	20 (36%)	36	0.0295 (1.00)	0.512 (1.00)	0.299 (1.00)	0.113 (1.00)	0.231 (1.00)	0.0656 (1.00)	0.465 (1.00)	0.179 (1.00)
amp 3q26 2	37 (66%)	19	0.00151 (0.741)	0.00516 (1.00)	0.09 (1.00)	0.156 (1.00)	0.349 (1.00)	0.242 (1.00)	0.731 (1.00)	0.107 (1.00)
amp 4p16 3	25 (45%)	31	0.03 (1.00)	0.131 (1.00)	0.386 (1.00)	0.19 (1.00)	0.976 (1.00)	0.29 (1.00)	0.877 (1.00)	0.666 (1.00)
amp 5p13 2	26 (46%)	30	0.0574 (1.00)	0.572 (1.00)	0.245 (1.00)	0.0561 (1.00)	0.929 (1.00)	0.0456 (1.00)	0.976 (1.00)	0.141 (1.00)
amp 6p24 2	37 (66%)	19	0.109 (1.00)	0.971 (1.00)	0.688 (1.00)	0.36 (1.00)	0.874 (1.00)	0.5 (1.00)	0.861 (1.00)	0.576 (1.00)
amp 8p11 21	33 (59%)	23	0.374 (1.00)	0.627 (1.00)	0.68 (1.00)	0.557 (1.00)	0.622 (1.00)	1 (1.00)	0.791 (1.00)	0.955 (1.00)
amp 8q11 23	38 (68%)	18	0.147 (1.00)	0.226 (1.00)	0.2 (1.00)	0.164 (1.00)	0.771 (1.00)	0.922 (1.00)	0.729 (1.00)	0.958 (1.00)
amp 8q24 21	42 (75%)	14	0.0438 (1.00)	0.757 (1.00)	0.189 (1.00)	0.34 (1.00)	0.0383 (1.00)	0.0317 (1.00)	0.0168 (1.00)	0.0627 (1.00)
amp 8q24 21	40 (71%)	16	0.00741 (1.00)	0.357 (1.00)	0.0802 (1.00)	0.117 (1.00)	0.0485 (1.00)	0.0629 (1.00)	0.018 (1.00)	0.106 (1.00)
amp 10q22 2	26 (46%)	30	0.246 (1.00)	0.492 (1.00)	0.965 (1.00)	0.923 (1.00)	0.726 (1.00)	0.74 (1.00)	0.599 (1.00)	0.72 (1.00)
amp 11q13 1	19 (34%)	37	0.461 (1.00)	0.648 (1.00)	0.327 (1.00)	0.302 (1.00)	0.76 (1.00)	1 (1.00)	0.67 (1.00)	0.869 (1.00)
amp 12q12	22 (39%)	34	0.162 (1.00)	0.107 (1.00)	0.253 (1.00)	0.403 (1.00)	0.928 (1.00)	1 (1.00)	0.689 (1.00)	0.795 (1.00)
amp 12q15	17 (30%)	39	0.469 (1.00)	0.378 (1.00)	0.252 (1.00)	0.702 (1.00)	0.799 (1.00)	0.166 (1.00)	0.556 (1.00)	0.572 (1.00)
amp 13q31 3	25 (45%)	31	0.407 (1.00)	0.443 (1.00)	0.139 (1.00)	0.117 (1.00)	0.0865 (1.00)	0.0374 (1.00)	0.0308 (1.00)	0.0407 (1.00)
amp 16p11 2	20 (36%)	36	0.00455 (1.00)	0.28 (1.00)	0.655 (1.00)	0.0729 (1.00)	0.76 (1.00)	0.411 (1.00)	0.402 (1.00)	0.141 (1.00)
amp 17q12	27 (48%)	29	0.939 (1.00)	0.189 (1.00)	0.334 (1.00)	0.458 (1.00)	0.343 (1.00)	0.785 (1.00)	0.639 (1.00)	1 (1.00)
amp 17q25 1	32 (57%)	24	0.64 (1.00)	0.0122 (1.00)	0.632 (1.00)	0.307 (1.00)	0.687 (1.00)	0.721 (1.00)	0.504 (1.00)	0.756 (1.00)
amp 19p13 2	19 (34%)	37	0.394 (1.00)	0.271 (1.00)	0.797 (1.00)	0.323 (1.00)	0.346 (1.00)	0.275 (1.00)	0.215 (1.00)	0.665 (1.00)
amp 20q11 21	48 (86%)	8	0.0141 (1.00)	0.167 (1.00)	0.544 (1.00)	0.423 (1.00)	0.161 (1.00)	0.144 (1.00)	0.128 (1.00)	0.192 (1.00)
amp 20q11 21	48 (86%)	8	0.155 (1.00)	0.255 (1.00)	0.193 (1.00)	0.316 (1.00)	0.178 (1.00)	0.352 (1.00)	0.147 (1.00)	0.572 (1.00)
amp xp11 21	28 (50%)	28	0.268 (1.00)	0.566 (1.00)	0.0488 (1.00)	0.3 (1.00)	0.0285 (1.00)	0.0997 (1.00)	0.0813 (1.00)	0.088 (1.00)
del 1p36 21	19 (34%)	37	0.083 (1.00)	0.378 (1.00)	0.348 (1.00)	0.0816 (1.00)	0.135 (1.00)	0.0243 (1.00)	0.121 (1.00)	0.102 (1.00)
del 2q22 1	11 (20%)	45	0.502 (1.00)	0.545 (1.00)	0.526 (1.00)	0.171 (1.00)	0.551 (1.00)	0.555 (1.00)	0.284 (1.00)	0.162 (1.00)
del 3p21 1	37 (66%)	19	0.428 (1.00)	0.46 (1.00)	0.466 (1.00)	0.433 (1.00)	0.519 (1.00)	0.768 (1.00)	0.49 (1.00)	0.255 (1.00)
del 3p14 1	30 (54%)	26	1 (1.00)	0.651 (1.00)	0.172 (1.00)	0.619 (1.00)	0.0874 (1.00)	0.537 (1.00)	0.205 (1.00)	0.133 (1.00)
del 3q13 31	19 (34%)	37	0.117 (1.00)	0.0989 (1.00)	0.923 (1.00)	0.159 (1.00)	0.972 (1.00)	0.655 (1.00)	0.707 (1.00)	0.617 (1.00)
del 4q22 1	37 (66%)	19	0.0643 (1.00)	0.0555 (1.00)	0.0245 (1.00)	0.154 (1.00)	0.0124 (1.00)	0.125 (1.00)	0.0245 (1.00)	0.14 (1.00)
del 4q34 3	37 (66%)	19	0.00425 (1.00)	0.0198 (1.00)	0.011 (1.00)	0.0404 (1.00)	0.00298 (1.00)	0.201 (1.00)	0.00818 (1.00)	0.101 (1.00)
del 5q11 2	26 (46%)	30	0.153 (1.00)	0.0922 (1.00)	0.585 (1.00)	0.45 (1.00)	0.549 (1.00)	0.295 (1.00)	0.0779 (1.00)	0.12 (1.00)
del 6q26	10 (18%)	46	0.528 (1.00)	0.543 (1.00)	0.121 (1.00)	0.701 (1.00)	0.33 (1.00)	0.3 (1.00)	0.174 (1.00)	0.719 (1.00)
del 7q11 22	12 (21%)	44	0.265 (1.00)	0.509 (1.00)	0.761 (1.00)	0.834 (1.00)	0.861 (1.00)	0.533 (1.00)	0.808 (1.00)	0.876 (1.00)
del 7q36 2	20 (36%)	36	0.169 (1.00)	0.169 (1.00)	0.494 (1.00)	0.273 (1.00)	0.401 (1.00)	0.0458 (1.00)	0.548 (1.00)	0.265 (1.00)
del 8p21 3	32 (57%)	24	0.00064 (0.316)	0.45 (1.00)	0.267 (1.00)	0.327 (1.00)	0.812 (1.00)	0.287 (1.00)	0.443 (1.00)	0.707 (1.00)
del 9p23	34 (61%)	22	0.0948 (1.00)	0.122 (1.00)	0.636 (1.00)	0.325 (1.00)	0.503 (1.00)	0.425 (1.00)	0.889 (1.00)	0.25 (1.00)
del 9q21 13	39 (70%)	17	0.108 (1.00)	0.324 (1.00)	0.212 (1.00)	0.254 (1.00)	0.479 (1.00)	0.32 (1.00)	0.678 (1.00)	0.653 (1.00)
del 9q33 3	38 (68%)	18	0.448 (1.00)	0.0663 (1.00)	0.087 (1.00)	0.169 (1.00)	1 (1.00)	0.103 (1.00)	0.856 (1.00)	0.447 (1.00)
del 10q21 1	18 (32%)	38	0.561 (1.00)	0.397 (1.00)	0.603 (1.00)	0.318 (1.00)	0.47 (1.00)	0.293 (1.00)	0.312 (1.00)	0.554 (1.00)
del 10q23 31	20 (36%)	36	0.142 (1.00)	0.103 (1.00)	0.123 (1.00)	0.246 (1.00)	0.76 (1.00)	0.853 (1.00)	0.591 (1.00)	0.906 (1.00)
del 11p15 5	25 (45%)	31	0.19 (1.00)	0.766 (1.00)	0.899 (1.00)	0.895 (1.00)	0.726 (1.00)	0.897 (1.00)	0.239 (1.00)	0.831 (1.00)
del 11q14 1	26 (46%)	30	0.648 (1.00)	0.216 (1.00)	1 (1.00)	0.922 (1.00)	0.268 (1.00)	0.525 (1.00)	0.261 (1.00)	0.293 (1.00)
del 11q24 2	27 (48%)	29	0.565 (1.00)	0.0315 (1.00)	0.139 (1.00)	0.784 (1.00)	0.248 (1.00)	0.621 (1.00)	0.253 (1.00)	0.281 (1.00)
del 12q23 1	20 (36%)	36	0.661 (1.00)	0.898 (1.00)	0.655 (1.00)	0.75 (1.00)	0.95 (1.00)	0.34 (1.00)	0.929 (1.00)	0.65 (1.00)
del 12q24 31	20 (36%)	36	0.813 (1.00)	0.825 (1.00)	0.155 (1.00)	0.259 (1.00)	0.562 (1.00)	0.887 (1.00)	0.15 (1.00)	0.914 (1.00)
del 13q12 11	30 (54%)	26	0.468 (1.00)	0.0198 (1.00)	0.373 (1.00)	0.208 (1.00)	0.723 (1.00)	0.0256 (1.00)	0.487 (1.00)	0.0876 (1.00)
del 14q21 1	28 (50%)	28	0.732 (1.00)	0.0499 (1.00)	0.0632 (1.00)	0.0561 (1.00)	0.38 (1.00)	0.379 (1.00)	0.355 (1.00)	0.663 (1.00)
del 15q15 1	43 (77%)	13	0.0399 (1.00)	0.0312 (1.00)	0.348 (1.00)	0.768 (1.00)	0.117 (1.00)	0.345 (1.00)	0.0493 (1.00)	0.243 (1.00)
del 16p13 3	33 (59%)	23	0.163 (1.00)	0.551 (1.00)	0.569 (1.00)	0.228 (1.00)	0.347 (1.00)	0.39 (1.00)	0.604 (1.00)	0.173 (1.00)
del 16q23 1	39 (70%)	17	0.161 (1.00)	0.422 (1.00)	0.398 (1.00)	0.393 (1.00)	0.867 (1.00)	0.812 (1.00)	0.479 (1.00)	0.98 (1.00)
del 17p13 1	42 (75%)	14	0.0678 (1.00)	0.0554 (1.00)	0.0581 (1.00)	0.425 (1.00)	0.132 (1.00)	0.182 (1.00)	0.0625 (1.00)	0.123 (1.00)
del 17q21 32	19 (34%)	37	0.87 (1.00)	0.763 (1.00)	0.175 (1.00)	0.0663 (1.00)	0.223 (1.00)	0.209 (1.00)	0.186 (1.00)	0.297 (1.00)
del 18q22 2	26 (46%)	30	0.134 (1.00)	0.342 (1.00)	0.505 (1.00)	0.362 (1.00)	0.0224 (1.00)	0.0795 (1.00)	0.0896 (1.00)	0.231 (1.00)
del 19p13 3	47 (84%)	9	0.142 (1.00)	0.02 (1.00)	0.0981 (1.00)	0.38 (1.00)	0.0148 (1.00)	0.0849 (1.00)	0.00856 (1.00)	0.16 (1.00)
del 19q13 33	17 (30%)	39	0.0381 (1.00)	0.00896 (1.00)	0.00064 (0.316)	0.0358 (1.00)	0.222 (1.00)	0.0379 (1.00)	0.558 (1.00)	0.0162 (1.00)
del 20p12 1	9 (16%)	47	1 (1.00)	0.699 (1.00)	0.389 (1.00)	0.53 (1.00)	0.221 (1.00)	0.339 (1.00)	0.318 (1.00)	0.595 (1.00)
del 22q13 31	40 (71%)	16	0.584 (1.00)	0.408 (1.00)	0.892 (1.00)	0.456 (1.00)	0.576 (1.00)	0.351 (1.00)	0.485 (1.00)	0.727 (1.00)
del xp21 1	18 (32%)	38	0.6 (1.00)	0.421 (1.00)	0.821 (1.00)	0.87 (1.00)	0.361 (1.00)	1 (1.00)	0.781 (1.00)	0.656 (1.00)
del xq25	23 (41%)	33	0.554 (1.00)	0.311 (1.00)	0.112 (1.00)	0.899 (1.00)	0.731 (1.00)	0.566 (1.00)	0.566 (1.00)	0.506 (1.00)

'amp_19q12' versus 'METHLYATION_CNMF'

P value = 8e-05 (Fisher's exact test), Q value = 0.04

Table S1. Gene #22: 'amp_19q12' versus Molecular Subtype #2: 'METHLYATION_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3	CLUS_4	CLUS_5
ALL	11	9	10	13	13
AMP PEAK 22(19Q12) MUTATED	11	7	3	11	13
AMP PEAK 22(19Q12) WILD-TYPE	0	2	7	2	0

Figure S1. Get High-res Image Gene #22: 'amp_19q12' versus Molecular Subtype #2: 'METHLYATION_CNMF'

'del_13q14.2' versus 'METHLYATION_CNMF'

P value = 0.00045 (Fisher's exact test), Q value = 0.22

Table S2. Gene #49: 'del_13q14.2' versus Molecular Subtype #2: 'METHLYATION_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3	CLUS_4	CLUS_5
ALL	11	9	10	13	13
DEL PEAK 24(13Q14.2) MUTATED	3	7	7	12	3
DEL PEAK 24(13Q14.2) WILD-TYPE	8	2	3	1	10

Figure S2. Get High-res Image Gene #49: 'del_13q14.2' versus Molecular Subtype #2: 'METHLYATION_CNMF'

Methods & Data

Input

Copy number data file = transformed.cor.cli.txt
Molecular subtype file = UCS-TP.transferedmergedcluster.txt
Number of patients = 56
Number of significantly focal cnvs = 62
Number of molecular subtypes = 8
Exclude genes that fewer than K tumors have alterations, 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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