Correlation between copy number variation genes and molecular subtypes

Esophageal Carcinoma (Primary solid tumor)

23 September 2013 | analyses__2013_09_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 variation genes and molecular subtypes. Broad Institute of MIT and Harvard. doi:10.7908/C1D50K9K

Overview

Introduction

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

Summary

Testing the association between copy number variation of 65 peak regions and 2 molecular subtypes across 63 patients, 6 significant findings detected with Q value < 0.25.

Amp Peak 4(3q26.2) cnvs correlated to 'CN_CNMF' and 'METHLYATION_CNMF'.
Amp Peak 14(11q13.3) cnvs correlated to 'CN_CNMF'.
Amp Peak 15(12p13.33) cnvs correlated to 'CN_CNMF' and 'METHLYATION_CNMF'.
Del Peak 24(11q24.3) cnvs correlated to 'CN_CNMF'.

Results

Overview of the results

Table 1. Get Full Table Overview of the association between significant copy number variation of 65 regions and 2 molecular subtypes. Shown in the table are P values (Q values). Thresholded by Q value < 0.25, 6 significant findings detected.


		Molecular subtypes	CN CNMF	METHLYATION CNMF
	nCNV (%)	nWild-Type	Fisher's exact test	Fisher's exact test
Amp Peak 4(3q26 2)	0 (0%)	15	4.6e-05 (0.00598)	0.000153 (0.0197)
Amp Peak 15(12p13 33)	0 (0%)	32	0.00149 (0.187)	0.000806 (0.103)
Amp Peak 14(11q13 3)	0 (0%)	24	0.00166 (0.207)	0.00596 (0.739)
Del Peak 24(11q24 3)	0 (0%)	33	0.00108 (0.137)	0.72 (1.00)
Amp Peak 1(1p34 2)	0 (0%)	50	0.354 (1.00)	0.44 (1.00)
Amp Peak 2(1q42 3)	0 (0%)	30	0.0713 (1.00)	0.0508 (1.00)
Amp Peak 3(2q14 2)	0 (0%)	43	0.0924 (1.00)	0.167 (1.00)
Amp Peak 5(5p15 33)	0 (0%)	24	0.274 (1.00)	0.172 (1.00)
Amp Peak 6(6p21 1)	0 (0%)	46	0.15 (1.00)	0.933 (1.00)
Amp Peak 7(6q12)	0 (0%)	48	0.526 (1.00)	1 (1.00)
Amp Peak 8(7p11 2)	0 (0%)	19	1 (1.00)	0.88 (1.00)
Amp Peak 9(7q21 2)	0 (0%)	21	0.0219 (1.00)	0.349 (1.00)
Amp Peak 10(8p11 21)	0 (0%)	31	0.766 (1.00)	0.313 (1.00)
Amp Peak 11(8q24 21)	0 (0%)	10	0.183 (1.00)	0.0247 (1.00)
Amp Peak 12(10p11 21)	0 (0%)	48	0.526 (1.00)	0.741 (1.00)
Amp Peak 13(11p13)	0 (0%)	45	0.822 (1.00)	0.874 (1.00)
Amp Peak 16(12p12 1)	0 (0%)	28	0.0198 (1.00)	0.0239 (1.00)
Amp Peak 17(14q22 1)	0 (0%)	41	0.219 (1.00)	0.26 (1.00)
Amp Peak 18(17q12)	0 (0%)	40	0.0237 (1.00)	0.412 (1.00)
Amp Peak 19(17q24 3)	0 (0%)	35	0.305 (1.00)	0.413 (1.00)
Amp Peak 20(18p11 32)	0 (0%)	40	0.0237 (1.00)	0.588 (1.00)
Amp Peak 21(18q11 2)	0 (0%)	47	0.148 (1.00)	0.287 (1.00)
Amp Peak 22(19p13 2)	0 (0%)	49	0.375 (1.00)	0.306 (1.00)
Amp Peak 23(19p13 11)	0 (0%)	47	0.0272 (1.00)	0.609 (1.00)
Amp Peak 24(19q12)	0 (0%)	42	0.148 (1.00)	0.257 (1.00)
Amp Peak 25(Xp11 4)	0 (0%)	51	0.19 (1.00)	0.843 (1.00)
Del Peak 1(1p36 13)	0 (0%)	44	1 (1.00)	0.126 (1.00)
Del Peak 2(1p13 2)	0 (0%)	40	0.946 (1.00)	0.496 (1.00)
Del Peak 3(1q44)	0 (0%)	55	0.343 (1.00)	0.484 (1.00)
Del Peak 4(2q22 1)	0 (0%)	47	0.71 (1.00)	0.392 (1.00)
Del Peak 5(2q34)	0 (0%)	47	0.403 (1.00)	0.0423 (1.00)
Del Peak 6(3p26 1)	0 (0%)	18	0.168 (1.00)	0.0576 (1.00)
Del Peak 7(3p14 3)	0 (0%)	13	0.0108 (1.00)	0.0251 (1.00)
Del Peak 8(3p14 2)	0 (0%)	12	0.158 (1.00)	0.282 (1.00)
Del Peak 9(3q11 1)	0 (0%)	53	0.745 (1.00)	1 (1.00)
Del Peak 10(3q26 31)	0 (0%)	57	0.641 (1.00)	0.0916 (1.00)
Del Peak 11(4p15 2)	0 (0%)	28	0.653 (1.00)	0.845 (1.00)
Del Peak 12(4q22 1)	0 (0%)	32	0.657 (1.00)	0.849 (1.00)
Del Peak 13(5q11 2)	0 (0%)	26	0.44 (1.00)	0.00676 (0.832)
Del Peak 14(5q12 3)	0 (0%)	24	0.639 (1.00)	0.0168 (1.00)
Del Peak 15(6p25 3)	0 (0%)	39	0.946 (1.00)	0.276 (1.00)
Del Peak 16(6q14 2)	0 (0%)	47	0.307 (1.00)	0.806 (1.00)
Del Peak 17(7q31 1)	0 (0%)	42	0.167 (1.00)	0.832 (1.00)
Del Peak 18(7q36 2)	0 (0%)	36	0.23 (1.00)	0.895 (1.00)
Del Peak 19(8p23 2)	0 (0%)	34	0.122 (1.00)	0.545 (1.00)
Del Peak 20(9p21 3)	0 (0%)	11	0.0078 (0.951)	0.0237 (1.00)
Del Peak 21(10p11 21)	0 (0%)	44	0.253 (1.00)	0.111 (1.00)
Del Peak 22(10q23 31)	0 (0%)	33	0.146 (1.00)	0.213 (1.00)
Del Peak 23(11p15 4)	0 (0%)	35	0.0862 (1.00)	0.0693 (1.00)
Del Peak 25(12q12)	0 (0%)	46	0.722 (1.00)	0.761 (1.00)
Del Peak 26(13q12 11)	0 (0%)	33	0.0581 (1.00)	0.0726 (1.00)
Del Peak 27(15q13 1)	0 (0%)	45	0.822 (1.00)	0.587 (1.00)
Del Peak 28(16q23 1)	0 (0%)	39	0.0449 (1.00)	0.03 (1.00)
Del Peak 29(17q25 3)	0 (0%)	49	0.801 (1.00)	0.923 (1.00)
Del Peak 30(18q12 2)	0 (0%)	28	0.175 (1.00)	0.149 (1.00)
Del Peak 31(18q21 2)	0 (0%)	25	0.118 (1.00)	0.154 (1.00)
Del Peak 32(19p13 3)	0 (0%)	31	0.264 (1.00)	0.645 (1.00)
Del Peak 33(19q13 31)	0 (0%)	43	0.203 (1.00)	0.0111 (1.00)
Del Peak 34(20p12 1)	0 (0%)	55	0.168 (1.00)	0.484 (1.00)
Del Peak 35(21q22 12)	0 (0%)	26	0.283 (1.00)	0.283 (1.00)
Del Peak 36(22q11 1)	0 (0%)	37	0.269 (1.00)	0.0167 (1.00)
Del Peak 37(Xp22 2)	0 (0%)	36	0.42 (1.00)	0.804 (1.00)
Del Peak 38(Xp21 1)	0 (0%)	35	0.233 (1.00)	0.681 (1.00)
Del Peak 39(Xp11 3)	0 (0%)	32	0.145 (1.00)	0.72 (1.00)
Del Peak 40(Xq21 33)	0 (0%)	49	0.266 (1.00)	0.923 (1.00)

'Amp Peak 4(3q26.2)' versus 'CN_CNMF'

P value = 4.6e-05 (Fisher's exact test), Q value = 0.006

Table S1. Gene #4: 'Amp Peak 4(3q26.2)' versus Molecular Subtype #1: 'CN_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	22	15	26
AMP PEAK 4(3Q26.2) CNV	22	13	13
AMP PEAK 4(3Q26.2) WILD-TYPE	0	2	13

Figure S1. Get High-res Image Gene #4: 'Amp Peak 4(3q26.2)' versus Molecular Subtype #1: 'CN_CNMF'

'Amp Peak 4(3q26.2)' versus 'METHLYATION_CNMF'

P value = 0.000153 (Fisher's exact test), Q value = 0.02

Table S2. Gene #4: 'Amp Peak 4(3q26.2)' versus Molecular Subtype #2: 'METHLYATION_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	30	14	19
AMP PEAK 4(3Q26.2) CNV	29	10	9
AMP PEAK 4(3Q26.2) WILD-TYPE	1	4	10

Figure S2. Get High-res Image Gene #4: 'Amp Peak 4(3q26.2)' versus Molecular Subtype #2: 'METHLYATION_CNMF'

'Amp Peak 14(11q13.3)' versus 'CN_CNMF'

P value = 0.00166 (Fisher's exact test), Q value = 0.21

Table S3. Gene #14: 'Amp Peak 14(11q13.3)' versus Molecular Subtype #1: 'CN_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	22	15	26
AMP PEAK 14(11Q13.3) CNV	20	7	12
AMP PEAK 14(11Q13.3) WILD-TYPE	2	8	14

Figure S3. Get High-res Image Gene #14: 'Amp Peak 14(11q13.3)' versus Molecular Subtype #1: 'CN_CNMF'

'Amp Peak 15(12p13.33)' versus 'CN_CNMF'

P value = 0.00149 (Fisher's exact test), Q value = 0.19

Table S4. Gene #15: 'Amp Peak 15(12p13.33)' versus Molecular Subtype #1: 'CN_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	22	15	26
AMP PEAK 15(12P13.33) CNV	16	9	6
AMP PEAK 15(12P13.33) WILD-TYPE	6	6	20

Figure S4. Get High-res Image Gene #15: 'Amp Peak 15(12p13.33)' versus Molecular Subtype #1: 'CN_CNMF'

'Amp Peak 15(12p13.33)' versus 'METHLYATION_CNMF'

P value = 0.000806 (Fisher's exact test), Q value = 0.1

Table S5. Gene #15: 'Amp Peak 15(12p13.33)' versus Molecular Subtype #2: 'METHLYATION_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	30	14	19
AMP PEAK 15(12P13.33) CNV	22	5	4
AMP PEAK 15(12P13.33) WILD-TYPE	8	9	15

Figure S5. Get High-res Image Gene #15: 'Amp Peak 15(12p13.33)' versus Molecular Subtype #2: 'METHLYATION_CNMF'

'Del Peak 24(11q24.3)' versus 'CN_CNMF'

P value = 0.00108 (Fisher's exact test), Q value = 0.14

Table S6. Gene #49: 'Del Peak 24(11q24.3)' versus Molecular Subtype #1: 'CN_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	22	15	26
DEL PEAK 24(11Q24.3) CNV	17	3	10
DEL PEAK 24(11Q24.3) WILD-TYPE	5	12	16

Figure S6. Get High-res Image Gene #49: 'Del Peak 24(11q24.3)' versus Molecular Subtype #1: 'CN_CNMF'

Methods & Data

Input

Copy number data file = All Lesions File (all_lesions.conf_##.txt, where ## is the confidence level). The all lesions file is from GISTIC pipeline and summarizes the results from the GISTIC run. It contains data about the significant regions of amplification and deletion as well as which samples are amplified or deleted in each of these regions. The identified regions are listed down the first column, and the samples are listed across the first row, starting in column 10.
Molecular subtype file = ESCA-TP.transferedmergedcluster.txt
Number of patients = 63
Number of copy number variation regions = 65
Number of molecular subtypes = 2
Exclude regions 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)

[3] GISTIC_version2

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