Correlation between copy number variation genes (focal events) and selected clinical features
Mesothelioma (Primary solid tumor)
28 January 2016 | analyses__2016_01_28
Maintainer Information
Citation Information
doi:10.7908/C15D8R8G
Maintained by TCGA GDAC Team (Broad Institute/MD Anderson Cancer Center/Harvard Medical School)
Cite as Broad Institute TCGA Genome Data Analysis Center (2016): Correlation between copy number variation genes (focal events) and selected clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C15D8R8G
Overview
Introduction

This pipeline computes the correlation between significant copy number variation (cnv focal) genes and selected clinical features.

Summary

Testing the association between copy number variation 21 focal events and 11 clinical features across 87 patients, 15 significant findings detected with Q value < 0.25.

- del_1p36.31 cnv correlated to 'Time to Death'.

- del_2q35 cnv correlated to 'Time to Death' and 'GENDER'.

- del_3p21.1 cnv correlated to 'KARNOFSKY_PERFORMANCE_SCORE'.

- del_4q26 cnv correlated to 'Time to Death'.

- del_4q34.3 cnv correlated to 'Time to Death'.

- del_5q23.2 cnv correlated to 'Time to Death'.

- del_9p21.3 cnv correlated to 'Time to Death'.

- del_10p15.3 cnv correlated to 'Time to Death' and 'RADIATION_THERAPY'.

- del_10q25.2 cnv correlated to 'Time to Death'.

- del_14q32.31 cnv correlated to 'Time to Death'.

- del_15q15.1 cnv correlated to 'Time to Death' and 'KARNOFSKY_PERFORMANCE_SCORE'.

- del_16q24.1 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 21 focal events and 11 clinical features. Shown in the table are P values (Q values). Thresholded by Q value < 0.25, 15 significant findings detected.

|  | Clinical Features | Time to Death | YEARS TO BIRTH | PATHOLOGIC STAGE | PATHOLOGY T STAGE | PATHOLOGY N STAGE | PATHOLOGY M STAGE | GENDER | RADIATION THERAPY | KARNOFSKY PERFORMANCE SCORE | HISTOLOGICAL TYPE | RESIDUAL TUMOR
| 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 | Wilcoxon-test | Fisher's exact test | Fisher's exact test
del 2q35 | 17 (20%) | 70 | 0.00831 (0.174) | 0.397 (0.882) | 0.766 (1.00) | 0.82 (1.00) | 0.313 (0.797) | 0.566 (0.932) | 0.0129 (0.213) | 0.376 (0.851) |  | 0.655 (0.964) | 0.319 (0.8)
del 10p15 3 | 28 (32%) | 59 | 6.76e-07 (9.72e-05) | 0.598 (0.946) | 0.036 (0.397) | 0.186 (0.711) | 0.367 (0.851) | 0.551 (0.932) | 1 (1.00) | 0.00408 (0.106) | 0.058 (0.446) | 0.102 (0.589) | 0.211 (0.743)
del 15q15 1 | 28 (32%) | 59 | 0.000648 (0.0374) | 0.993 (1.00) | 0.561 (0.932) | 0.764 (1.00) | 0.888 (1.00) | 1 (1.00) | 1 (1.00) | 0.801 (1.00) | 0.00382 (0.106) | 0.191 (0.711) | 0.42 (0.903)
del 1p36 31 | 33 (38%) | 54 | 0.000204 (0.0157) | 0.93 (1.00) | 0.956 (1.00) | 0.644 (0.959) | 0.949 (1.00) | 0.268 (0.764) | 0.776 (1.00) | 0.804 (1.00) | 0.0751 (0.469) | 0.935 (1.00) | 0.818 (1.00)
del 3p21 1 | 48 (55%) | 39 | 0.884 (1.00) | 0.864 (1.00) | 0.224 (0.743) | 0.703 (0.99) | 0.672 (0.971) | 1 (1.00) | 0.782 (1.00) | 0.813 (1.00) | 0.0102 (0.197) | 0.179 (0.711) | 0.824 (1.00)
del 4q26 | 38 (44%) | 49 | 0.00112 (0.052) | 0.566 (0.932) | 0.388 (0.87) | 0.106 (0.589) | 0.447 (0.924) | 0.251 (0.762) | 0.28 (0.779) | 0.477 (0.932) | 0.0471 (0.409) | 0.151 (0.648) | 0.131 (0.633)
del 4q34 3 | 41 (47%) | 46 | 0.00453 (0.106) | 0.147 (0.648) | 0.634 (0.953) | 0.31 (0.797) | 0.546 (0.932) | 0.238 (0.743) | 0.58 (0.932) | 1 (1.00) | 0.0471 (0.409) | 0.304 (0.797) | 0.0778 (0.473)
del 5q23 2 | 17 (20%) | 70 | 0.00239 (0.0919) | 0.249 (0.762) | 1 (1.00) | 0.52 (0.932) | 1 (1.00) | 0.462 (0.932) | 0.179 (0.711) | 0.228 (0.743) | 0.0751 (0.469) | 0.875 (1.00) | 0.448 (0.924)
del 9p21 3 | 51 (59%) | 36 | 8.42e-07 (9.72e-05) | 0.41 (0.893) | 0.765 (1.00) | 0.447 (0.924) | 0.668 (0.971) | 0.0672 (0.469) | 1 (1.00) | 1 (1.00) | 0.801 (1.00) | 0.649 (0.962) | 0.853 (1.00)
del 10q25 2 | 31 (36%) | 56 | 0.00458 (0.106) | 0.776 (1.00) | 0.725 (1.00) | 0.585 (0.932) | 0.716 (1.00) | 0.255 (0.764) | 1 (1.00) | 0.616 (0.953) | 0.131 (0.633) | 0.62 (0.953) | 0.482 (0.932)
del 14q32 31 | 39 (45%) | 48 | 0.0116 (0.206) | 0.932 (1.00) | 0.481 (0.932) | 0.14 (0.647) | 0.67 (0.971) | 0.238 (0.743) | 0.0503 (0.415) | 1 (1.00) | 0.0207 (0.266) | 0.0266 (0.307) | 0.126 (0.633)
del 16q24 1 | 22 (25%) | 65 | 0.0142 (0.219) | 0.721 (1.00) | 0.626 (0.953) | 0.969 (1.00) | 0.224 (0.743) | 0.545 (0.932) | 0.107 (0.589) | 0.58 (0.932) |  | 0.181 (0.711) | 0.263 (0.764)
del 1p21 3 | 37 (43%) | 50 | 0.0265 (0.307) | 0.298 (0.797) | 0.314 (0.797) | 0.128 (0.633) | 0.355 (0.845) | 1 (1.00) | 0.581 (0.932) | 0.23 (0.743) | 0.152 (0.648) | 0.967 (1.00) | 0.964 (1.00)
del 6q22 1 | 41 (47%) | 46 | 0.574 (0.932) | 0.848 (1.00) | 0.14 (0.647) | 0.832 (1.00) | 0.577 (0.932) | 0.565 (0.932) | 0.422 (0.903) | 0.342 (0.831) | 0.574 (0.932) | 0.763 (1.00) | 0.529 (0.932)
del 6q26 | 36 (41%) | 51 | 0.223 (0.743) | 0.87 (1.00) | 0.236 (0.743) | 0.816 (1.00) | 0.0737 (0.469) | 0.268 (0.764) | 1 (1.00) | 0.467 (0.932) | 0.683 (0.971) | 0.856 (1.00) | 0.791 (1.00)
del 8p23 2 | 18 (21%) | 69 | 0.426 (0.903) | 0.294 (0.797) | 0.335 (0.823) | 0.16 (0.672) | 0.755 (1.00) | 1 (1.00) | 0.506 (0.932) | 0.566 (0.932) | 0.0751 (0.469) | 0.264 (0.764) | 0.232 (0.743)
del 11q23 2 | 18 (21%) | 69 | 0.0657 (0.469) | 0.626 (0.953) | 0.184 (0.711) | 0.55 (0.932) | 1 (1.00) | 0.558 (0.932) | 0.506 (0.932) | 0.548 (0.932) |  | 0.307 (0.797) | 0.348 (0.837)
del 12p13 31 | 11 (13%) | 76 | 0.0184 (0.266) | 0.361 (0.85) | 0.375 (0.851) | 0.939 (1.00) | 0.585 (0.932) | 1 (1.00) | 0.681 (0.971) | 0.278 (0.779) |  | 0.194 (0.711) | 0.193 (0.711)
del 13q14 11 | 44 (51%) | 43 | 0.0207 (0.266) | 0.575 (0.932) | 0.0466 (0.409) | 0.62 (0.953) | 0.0378 (0.397) | 0.237 (0.743) | 0.103 (0.589) | 0.633 (0.953) | 0.838 (1.00) | 0.904 (1.00) | 0.58 (0.932)
del 16p13 3 | 6 (7%) | 81 | 0.753 (1.00) | 0.0425 (0.409) | 0.128 (0.633) | 0.0478 (0.409) | 0.583 (0.932) | 1 (1.00) | 0.304 (0.797) | 1 (1.00) |  | 0.0674 (0.469) | 0.132 (0.633)
del 22q12 2 | 68 (78%) | 19 | 0.0529 (0.421) | 0.825 (1.00) | 0.409 (0.893) | 0.151 (0.648) | 0.869 (1.00) | 0.556 (0.932) | 0.327 (0.813) | 0.569 (0.932) | 0.635 (0.953) | 0.37 (0.851) | 0.685 (0.971)

'del_1p36.31' versus 'Time to Death'

P value = 0.000204 (logrank test), Q value = 0.016

Table S1. Gene #1: 'del_1p36.31' versus Clinical Feature #1: 'Time to Death'

| nPatients | nDeath | Duration Range (Median), Month
--- | --- | --- | ---
ALL | 85 | 73 | 0.7 - 91.7 (17.3)
DEL PEAK 1(1P36.31) MUTATED | 32 | 31 | 1.3 - 49.0 (12.2)
DEL PEAK 1(1P36.31) WILD-TYPE | 53 | 42 | 0.7 - 91.7 (22.6)

Figure S1. Get High-res Image Gene #1: 'del_1p36.31' versus Clinical Feature #1: 'Time to Death'

'del_2q35' versus 'Time to Death'

P value = 0.00831 (logrank test), Q value = 0.17

Table S2. Gene #3: 'del_2q35' versus Clinical Feature #1: 'Time to Death'

| nPatients | nDeath | Duration Range (Median), Month
--- | --- | --- | ---
ALL | 85 | 73 | 0.7 - 91.7 (17.3)
DEL PEAK 3(2Q35) MUTATED | 17 | 17 | 1.9 - 29.1 (12.7)
DEL PEAK 3(2Q35) WILD-TYPE | 68 | 56 | 0.7 - 91.7 (18.7)

Figure S2. Get High-res Image Gene #3: 'del_2q35' versus Clinical Feature #1: 'Time to Death'

'del_2q35' versus 'GENDER'

P value = 0.0129 (Fisher's exact test), Q value = 0.21

Table S3. Gene #3: 'del_2q35' versus Clinical Feature #7: 'GENDER'

nPatients | FEMALE | MALE
--- | --- | ---
ALL | 16 | 71
DEL PEAK 3(2Q35) MUTATED | 7 | 10
DEL PEAK 3(2Q35) WILD-TYPE | 9 | 61

Figure S3. Get High-res Image Gene #3: 'del_2q35' versus Clinical Feature #7: 'GENDER'

'del_3p21.1' versus 'KARNOFSKY_PERFORMANCE_SCORE'

P value = 0.0102 (Wilcoxon-test), Q value = 0.2

Table S4. Gene #4: 'del_3p21.1' versus Clinical Feature #9: 'KARNOFSKY_PERFORMANCE_SCORE'

| nPatients | Mean (Std.Dev)
--- | --- | ---
ALL | 17 | 77.6 (31.5)
DEL PEAK 4(3P21.1) MUTATED | 9 | 93.3 (7.1)
DEL PEAK 4(3P21.1) WILD-TYPE | 8 | 60.0 (39.3)

Figure S4. Get High-res Image Gene #4: 'del_3p21.1' versus Clinical Feature #9: 'KARNOFSKY_PERFORMANCE_SCORE'

'del_4q26' versus 'Time to Death'

P value = 0.00112 (logrank test), Q value = 0.052

Table S5. Gene #5: 'del_4q26' versus Clinical Feature #1: 'Time to Death'

| nPatients | nDeath | Duration Range (Median), Month
--- | --- | --- | ---
ALL | 85 | 73 | 0.7 - 91.7 (17.3)
DEL PEAK 5(4Q26) MUTATED | 38 | 36 | 1.9 - 68.7 (13.5)
DEL PEAK 5(4Q26) WILD-TYPE | 47 | 37 | 0.7 - 91.7 (23.6)

Figure S5. Get High-res Image Gene #5: 'del_4q26' versus Clinical Feature #1: 'Time to Death'

'del_4q34.3' versus 'Time to Death'

P value = 0.00453 (logrank test), Q value = 0.11

Table S6. Gene #6: 'del_4q34.3' versus Clinical Feature #1: 'Time to Death'

| nPatients | nDeath | Duration Range (Median), Month
--- | --- | --- | ---
ALL | 85 | 73 | 0.7 - 91.7 (17.3)
DEL PEAK 6(4Q34.3) MUTATED | 41 | 38 | 2.5 - 68.7 (13.6)
DEL PEAK 6(4Q34.3) WILD-TYPE | 44 | 35 | 0.7 - 91.7 (23.8)

Figure S6. Get High-res Image Gene #6: 'del_4q34.3' versus Clinical Feature #1: 'Time to Death'

'del_5q23.2' versus 'Time to Death'

P value = 0.00239 (logrank test), Q value = 0.092

Table S7. Gene #7: 'del_5q23.2' versus Clinical Feature #1: 'Time to Death'

| nPatients | nDeath | Duration Range (Median), Month
--- | --- | --- | ---
ALL | 85 | 73 | 0.7 - 91.7 (17.3)
DEL PEAK 7(5Q23.2) MUTATED | 17 | 17 | 3.5 - 41.5 (11.9)
DEL PEAK 7(5Q23.2) WILD-TYPE | 68 | 56 | 0.7 - 91.7 (20.1)

Figure S7. Get High-res Image Gene #7: 'del_5q23.2' versus Clinical Feature #1: 'Time to Death'

'del_9p21.3' versus 'Time to Death'

P value = 8.42e-07 (logrank test), Q value = 9.7e-05

Table S8. Gene #11: 'del_9p21.3' versus Clinical Feature #1: 'Time to Death'

| nPatients | nDeath | Duration Range (Median), Month
--- | --- | --- | ---
ALL | 85 | 73 | 0.7 - 91.7 (17.3)
DEL PEAK 11(9P21.3) MUTATED | 50 | 47 | 0.7 - 41.5 (13.0)
DEL PEAK 11(9P21.3) WILD-TYPE | 35 | 26 | 2.8 - 91.7 (27.2)

Figure S8. Get High-res Image Gene #11: 'del_9p21.3' versus Clinical Feature #1: 'Time to Death'

'del_10p15.3' versus 'Time to Death'

P value = 6.76e-07 (logrank test), Q value = 9.7e-05

Table S9. Gene #12: 'del_10p15.3' versus Clinical Feature #1: 'Time to Death'

| nPatients | nDeath | Duration Range (Median), Month
--- | --- | --- | ---
ALL | 85 | 73 | 0.7 - 91.7 (17.3)
DEL PEAK 12(10P15.3) MUTATED | 27 | 26 | 0.7 - 28.3 (10.8)
DEL PEAK 12(10P15.3) WILD-TYPE | 58 | 47 | 1.3 - 91.7 (23.5)

Figure S9. Get High-res Image Gene #12: 'del_10p15.3' versus Clinical Feature #1: 'Time to Death'

'del_10p15.3' versus 'RADIATION_THERAPY'

P value = 0.00408 (Fisher's exact test), Q value = 0.11

Table S10. Gene #12: 'del_10p15.3' versus Clinical Feature #8: 'RADIATION_THERAPY'

nPatients | NO | YES
--- | --- | ---
ALL | 62 | 24
DEL PEAK 12(10P15.3) MUTATED | 25 | 2
DEL PEAK 12(10P15.3) WILD-TYPE | 37 | 22

Figure S10. Get High-res Image Gene #12: 'del_10p15.3' versus Clinical Feature #8: 'RADIATION_THERAPY'

'del_10q25.2' versus 'Time to Death'

P value = 0.00458 (logrank test), Q value = 0.11

Table S11. Gene #13: 'del_10q25.2' versus Clinical Feature #1: 'Time to Death'

| nPatients | nDeath | Duration Range (Median), Month
--- | --- | --- | ---
ALL | 85 | 73 | 0.7 - 91.7 (17.3)
DEL PEAK 13(10Q25.2) MUTATED | 30 | 28 | 0.7 - 55.1 (11.7)
DEL PEAK 13(10Q25.2) WILD-TYPE | 55 | 45 | 1.3 - 91.7 (20.7)

Figure S11. Get High-res Image Gene #13: 'del_10q25.2' versus Clinical Feature #1: 'Time to Death'

'del_14q32.31' versus 'Time to Death'

P value = 0.0116 (logrank test), Q value = 0.21

Table S12. Gene #17: 'del_14q32.31' versus Clinical Feature #1: 'Time to Death'

| nPatients | nDeath | Duration Range (Median), Month
--- | --- | --- | ---
ALL | 85 | 73 | 0.7 - 91.7 (17.3)
DEL PEAK 17(14Q32.31) MUTATED | 38 | 35 | 1.3 - 77.6 (13.5)
DEL PEAK 17(14Q32.31) WILD-TYPE | 47 | 38 | 0.7 - 91.7 (21.8)

Figure S12. Get High-res Image Gene #17: 'del_14q32.31' versus Clinical Feature #1: 'Time to Death'

'del_15q15.1' versus 'Time to Death'

P value = 0.000648 (logrank test), Q value = 0.037

Table S13. Gene #18: 'del_15q15.1' versus Clinical Feature #1: 'Time to Death'

| nPatients | nDeath | Duration Range (Median), Month
--- | --- | --- | ---
ALL | 85 | 73 | 0.7 - 91.7 (17.3)
DEL PEAK 18(15Q15.1) MUTATED | 27 | 26 | 0.7 - 41.5 (12.7)
DEL PEAK 18(15Q15.1) WILD-TYPE | 58 | 47 | 1.9 - 91.7 (20.1)

Figure S13. Get High-res Image Gene #18: 'del_15q15.1' versus Clinical Feature #1: 'Time to Death'

'del_15q15.1' versus 'KARNOFSKY_PERFORMANCE_SCORE'

P value = 0.00382 (Wilcoxon-test), Q value = 0.11

Table S14. Gene #18: 'del_15q15.1' versus Clinical Feature #9: 'KARNOFSKY_PERFORMANCE_SCORE'

| nPatients | Mean (Std.Dev)
--- | --- | ---
ALL | 17 | 77.6 (31.5)
DEL PEAK 18(15Q15.1) MUTATED | 6 | 50.0 (41.0)
DEL PEAK 18(15Q15.1) WILD-TYPE | 11 | 92.7 (6.5)

Figure S14. Get High-res Image Gene #18: 'del_15q15.1' versus Clinical Feature #9: 'KARNOFSKY_PERFORMANCE_SCORE'

'del_16q24.1' versus 'Time to Death'

P value = 0.0142 (logrank test), Q value = 0.22

Table S15. Gene #20: 'del_16q24.1' versus Clinical Feature #1: 'Time to Death'

| nPatients | nDeath | Duration Range (Median), Month
--- | --- | --- | ---
ALL | 85 | 73 | 0.7 - 91.7 (17.3)
DEL PEAK 20(16Q24.1) MUTATED | 21 | 19 | 1.3 - 49.0 (14.7)
DEL PEAK 20(16Q24.1) WILD-TYPE | 64 | 54 | 0.7 - 91.7 (21.3)

Figure S15. Get High-res Image Gene #20: 'del_16q24.1' versus Clinical Feature #1: 'Time to Death'

Methods & Data
Input

- Copy number data file = all_lesions.txt from GISTIC pipeline

- Processed Copy number data file = /xchip/cga/gdac-prod/tcga-gdac/jobResults/GDAC_Correlate_Genomic_Events_Preprocess/MESO-TP/22533663/transformed.cor.cli.txt

- Clinical data file = /xchip/cga/gdac-prod/tcga-gdac/jobResults/Append_Data/MESO-TP/22507181/MESO-TP.merged_data.txt

- Number of patients = 87

- Number of significantly focal cnvs = 21

- Number of selected clinical features = 11

- Exclude genes 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.

- Analysis Results (MD5 checksum)

- Auxiliary Data (MD5 checksum)

- MAGE-TAB File (MD5 checksum)

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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