Correlation between copy number variation genes and molecular subtypes
Esophageal Carcinoma (Primary solid tumor)
23 May 2013 | analyses__2013_05_23
Maintainer Information
Citation Information
doi:10.7908/C1GM85B6
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/C1GM85B6
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 53 peak regions and 2 molecular subtypes across 50 patients, 3 significant findings detected with Q value < 0.25.

- Amp Peak 4(3q29) cnvs correlated to 'CN_CNMF' and 'METHLYATION_CNMF'.

- Amp Peak 13(11q13.3) 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 53 regions and 2 molecular subtypes. Shown in the table are P values (Q values). Thresholded by Q value < 0.25, 3 significant findings detected.

|  | Molecular subtypes | CN CNMF | METHLYATION CNMF
| nCNV (%) | nWild-Type | Fisher's exact test | Fisher's exact test
Amp Peak 4(3q29) | 0 (0%) | 12 | 0.000572 (0.0601) | 0.00223 (0.232)
Amp Peak 13(11q13 3) | 0 (0%) | 17 | 0.000123 (0.013) | 0.0219 (1.00)
Amp Peak 1(1p13 1) | 0 (0%) | 40 | 0.664 (1.00) | 0.481 (1.00)
Amp Peak 2(1q25 2) | 0 (0%) | 27 | 0.0403 (1.00) | 0.508 (1.00)
Amp Peak 3(2q14 2) | 0 (0%) | 33 | 0.645 (1.00) | 0.195 (1.00)
Amp Peak 5(6p21 1) | 0 (0%) | 37 | 0.101 (1.00) | 1 (1.00)
Amp Peak 6(6q12) | 0 (0%) | 40 | 0.291 (1.00) | 0.314 (1.00)
Amp Peak 7(7p11 2) | 0 (0%) | 14 | 0.852 (1.00) | 0.18 (1.00)
Amp Peak 8(7q21 3) | 0 (0%) | 15 | 0.114 (1.00) | 0.227 (1.00)
Amp Peak 9(8p11 21) | 0 (0%) | 23 | 0.515 (1.00) | 0.756 (1.00)
Amp Peak 10(8q24 21) | 0 (0%) | 7 | 0.0991 (1.00) | 0.137 (1.00)
Amp Peak 11(10p11 21) | 0 (0%) | 35 | 0.628 (1.00) | 0.852 (1.00)
Amp Peak 12(11p13) | 0 (0%) | 37 | 0.233 (1.00) | 1 (1.00)
Amp Peak 14(12p13 33) | 0 (0%) | 24 | 0.0358 (1.00) | 0.0313 (1.00)
Amp Peak 15(12p12 1) | 0 (0%) | 22 | 0.0661 (1.00) | 0.104 (1.00)
Amp Peak 16(17q24 3) | 0 (0%) | 26 | 0.212 (1.00) | 0.201 (1.00)
Amp Peak 17(18p11 32) | 0 (0%) | 32 | 0.389 (1.00) | 0.327 (1.00)
Amp Peak 18(18q11 2) | 0 (0%) | 36 | 0.41 (1.00) | 0.044 (1.00)
Amp Peak 19(19p13 2) | 0 (0%) | 38 | 0.284 (1.00) | 0.394 (1.00)
Amp Peak 20(19q12) | 0 (0%) | 31 | 0.0859 (1.00) | 0.135 (1.00)
Amp Peak 21(Xp11 4) | 0 (0%) | 40 | 0.291 (1.00) | 0.901 (1.00)
Del Peak 1(1p35 2) | 0 (0%) | 35 | 1 (1.00) | 0.852 (1.00)
Del Peak 2(1q44) | 0 (0%) | 42 | 0.485 (1.00) | 0.408 (1.00)
Del Peak 3(2q22 1) | 0 (0%) | 39 | 0.426 (1.00) | 0.612 (1.00)
Del Peak 4(2q37 2) | 0 (0%) | 37 | 0.461 (1.00) | 0.135 (1.00)
Del Peak 5(3p14 2) | 0 (0%) | 8 | 0.0854 (1.00) | 0.279 (1.00)
Del Peak 6(3q11 1) | 0 (0%) | 45 | 1 (1.00) | 0.84 (1.00)
Del Peak 7(3q26 31) | 0 (0%) | 46 | 0.159 (1.00) | 0.0388 (1.00)
Del Peak 8(4p15 2) | 0 (0%) | 21 | 0.296 (1.00) | 0.709 (1.00)
Del Peak 9(4q22 1) | 0 (0%) | 29 | 0.584 (1.00) | 0.239 (1.00)
Del Peak 10(5q11 2) | 0 (0%) | 20 | 0.44 (1.00) | 0.00275 (0.283)
Del Peak 11(5q12 3) | 0 (0%) | 18 | 0.608 (1.00) | 0.0079 (0.783)
Del Peak 12(6p25 3) | 0 (0%) | 30 | 0.875 (1.00) | 0.321 (1.00)
Del Peak 13(6q26) | 0 (0%) | 36 | 0.568 (1.00) | 0.277 (1.00)
Del Peak 14(7q31 1) | 0 (0%) | 33 | 0.36 (1.00) | 1 (1.00)
Del Peak 15(8p23 2) | 0 (0%) | 27 | 0.593 (1.00) | 0.873 (1.00)
Del Peak 16(9p21 3) | 0 (0%) | 10 | 0.0062 (0.626) | 0.0358 (1.00)
Del Peak 17(10p11 21) | 0 (0%) | 37 | 0.549 (1.00) | 0.0682 (1.00)
Del Peak 18(10q23 31) | 0 (0%) | 27 | 0.593 (1.00) | 0.24 (1.00)
Del Peak 19(11p15 4) | 0 (0%) | 26 | 0.818 (1.00) | 0.36 (1.00)
Del Peak 20(11q24 3) | 0 (0%) | 25 | 0.0465 (1.00) | 0.823 (1.00)
Del Peak 21(13q14 2) | 0 (0%) | 22 | 0.00641 (0.641) | 0.0321 (1.00)
Del Peak 22(15q13 1) | 0 (0%) | 36 | 0.616 (1.00) | 0.555 (1.00)
Del Peak 23(16q23 1) | 0 (0%) | 33 | 0.00336 (0.343) | 0.114 (1.00)
Del Peak 24(17q24 3) | 0 (0%) | 45 | 0.00862 (0.845) | 0.228 (1.00)
Del Peak 25(18q12 2) | 0 (0%) | 24 | 0.245 (1.00) | 0.176 (1.00)
Del Peak 26(19q13 31) | 0 (0%) | 33 | 0.333 (1.00) | 0.0647 (1.00)
Del Peak 27(20p12 1) | 0 (0%) | 42 | 0.485 (1.00) | 0.408 (1.00)
Del Peak 28(21q22 2) | 0 (0%) | 22 | 0.821 (1.00) | 0.812 (1.00)
Del Peak 29(22q11 1) | 0 (0%) | 30 | 0.0787 (1.00) | 0.0616 (1.00)
Del Peak 30(Xp21 1) | 0 (0%) | 26 | 0.632 (1.00) | 0.201 (1.00)
Del Peak 31(Xp11 3) | 0 (0%) | 25 | 0.725 (1.00) | 1 (1.00)
Del Peak 32(Xq21 33) | 0 (0%) | 38 | 0.839 (1.00) | 0.911 (1.00)

'Amp Peak 4(3q29)' versus 'CN_CNMF'

P value = 0.000572 (Fisher's exact test), Q value = 0.06

Table S1. Gene #4: 'Amp Peak 4(3q29)' versus Molecular Subtype #1: 'CN_CNMF'

nPatients | CLUS_1 | CLUS_2 | CLUS_3
--- | --- | --- | ---
ALL | 20 | 12 | 18
AMP PEAK 4(3Q29) CNV | 20 | 9 | 9
AMP PEAK 4(3Q29) WILD-TYPE | 0 | 3 | 9

Figure S1. Get High-res Image Gene #4: 'Amp Peak 4(3q29)' versus Molecular Subtype #1: 'CN_CNMF'

'Amp Peak 4(3q29)' versus 'METHLYATION_CNMF'

P value = 0.00223 (Fisher's exact test), Q value = 0.23

Table S2. Gene #4: 'Amp Peak 4(3q29)' versus Molecular Subtype #2: 'METHLYATION_CNMF'

nPatients | CLUS_1 | CLUS_2 | CLUS_3
--- | --- | --- | ---
ALL | 24 | 12 | 14
AMP PEAK 4(3Q29) CNV | 23 | 8 | 7
AMP PEAK 4(3Q29) WILD-TYPE | 1 | 4 | 7

Figure S2. Get High-res Image Gene #4: 'Amp Peak 4(3q29)' versus Molecular Subtype #2: 'METHLYATION_CNMF'

'Amp Peak 13(11q13.3)' versus 'CN_CNMF'

P value = 0.000123 (Fisher's exact test), Q value = 0.013

Table S3. Gene #13: 'Amp Peak 13(11q13.3)' versus Molecular Subtype #1: 'CN_CNMF'

nPatients | CLUS_1 | CLUS_2 | CLUS_3
--- | --- | --- | ---
ALL | 20 | 12 | 18
AMP PEAK 13(11Q13.3) CNV | 19 | 3 | 11
AMP PEAK 13(11Q13.3) WILD-TYPE | 1 | 9 | 7

Figure S3. Get High-res Image Gene #13: 'Amp Peak 13(11q13.3)' 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 = 50

- Number of copy number variation regions = 53

- 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

This is an experimental feature. The full results of the analysis summarized in this report can be downloaded from the TCGA Data Coordination Center.

- Analysis Results (MD5 checksum)

- Auxiliary Data (MD5 checksum)

- MAGE-TAB File (MD5 checksum)

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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