Brain Lower Grade Glioma: Correlation between copy number variation genes and selected clinical features
Maintained by TCGA GDAC Team (Broad Institute/MD Anderson Cancer Center/Harvard Medical School)
Overview
Introduction

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

Summary

Testing the association between copy number variation of 36 peak regions and 6 clinical features across 178 patients, 13 significant findings detected with Q value < 0.25.

- Amp Peak 1(1q32.1) cnvs correlated to 'AGE'.

- Amp Peak 4(7q32.3) cnvs correlated to 'AGE'.

- Amp Peak 9(12q14.1) cnvs correlated to 'Time to Death'.

- Amp Peak 10(19q13.2) cnvs correlated to 'Time to Death'.

- Del Peak 1(1p36.31) cnvs correlated to 'AGE', 'HISTOLOGICAL.TYPE', and 'RADIATIONS.RADIATION.REGIMENINDICATION'.

- Del Peak 11(9p21.3) cnvs correlated to 'Time to Death', 'AGE', and 'RADIATIONS.RADIATION.REGIMENINDICATION'.

- Del Peak 12(10q26.2) cnvs correlated to 'Time to Death'.

- Del Peak 17(14q24.3) cnvs correlated to 'Time to Death'.

- Del Peak 20(19q13.42) cnvs correlated to 'HISTOLOGICAL.TYPE'.

Results
Overview of the results

Table 1. Get Full Table Overview of the association between significant copy number variation of 36 regions and 6 clinical features. Shown in the table are P values (Q values). Thresholded by Q value < 0.25, 13 significant findings detected.

|  | Clinical Features | Time to Death | AGE | GENDER | KARNOFSKY PERFORMANCE SCORE | HISTOLOGICAL TYPE | RADIATIONS RADIATION REGIMENINDICATION
| nCNV (%) | nWild-Type | logrank test | t-test | Fisher's exact test | t-test | Fisher's exact test | Fisher's exact test
Del Peak 1(1p36 31) | 69 (39%) | 109 | 0.974 (1.00) | 0.000459 (0.0945) | 0.644 (1.00) | 0.934 (1.00) | 3.16e-10 (6.82e-08) | 0.000673 (0.138)
Del Peak 11(9p21 3) | 66 (37%) | 112 | 5.14e-05 (0.0109) | 0.000171 (0.0357) | 0.755 (1.00) | 0.328 (1.00) | 0.405 (1.00) | 4.37e-05 (0.00931)
Amp Peak 1(1q32 1) | 21 (12%) | 157 | 0.0626 (1.00) | 0.000363 (0.0751) | 0.357 (1.00) | 0.079 (1.00) | 0.508 (1.00) | 0.249 (1.00)
Amp Peak 4(7q32 3) | 65 (37%) | 113 | 0.349 (1.00) | 0.000236 (0.049) | 0.0277 (1.00) | 0.898 (1.00) | 0.612 (1.00) | 0.0188 (1.00)
Amp Peak 9(12q14 1) | 13 (7%) | 165 | 2.7e-05 (0.00578) | 0.0514 (1.00) | 0.562 (1.00) | 0.492 (1.00) | 0.127 (1.00) | 0.774 (1.00)
Amp Peak 10(19q13 2) | 12 (7%) | 166 | 7.69e-05 (0.0162) | 0.00175 (0.355) | 1 (1.00) | 0.497 (1.00) | 0.696 (1.00) | 0.147 (1.00)
Del Peak 12(10q26 2) | 56 (31%) | 122 | 0.000139 (0.0292) | 0.00873 (1.00) | 0.105 (1.00) | 0.366 (1.00) | 0.104 (1.00) | 0.419 (1.00)
Del Peak 17(14q24 3) | 45 (25%) | 133 | 0.000758 (0.155) | 0.121 (1.00) | 0.0233 (1.00) | 0.961 (1.00) | 0.195 (1.00) | 0.606 (1.00)
Del Peak 20(19q13 42) | 100 (56%) | 78 | 0.0155 (1.00) | 0.515 (1.00) | 0.879 (1.00) | 0.622 (1.00) | 1.86e-06 (4e-04) | 0.65 (1.00)
Amp Peak 2(4q12) | 8 (4%) | 170 | 0.876 (1.00) | 0.836 (1.00) | 0.289 (1.00) | 0.319 (1.00) | 0.0202 (1.00) | 0.727 (1.00)
Amp Peak 3(7p11 2) | 47 (26%) | 131 | 0.00607 (1.00) | 0.00554 (1.00) | 0.121 (1.00) | 0.563 (1.00) | 0.266 (1.00) | 0.127 (1.00)
Amp Peak 5(8q24 21) | 36 (20%) | 142 | 0.92 (1.00) | 0.633 (1.00) | 0.258 (1.00) | 0.31 (1.00) | 0.0877 (1.00) | 0.0952 (1.00)
Amp Peak 6(10p15 1) | 29 (16%) | 149 | 0.674 (1.00) | 0.00907 (1.00) | 0.413 (1.00) | 0.664 (1.00) | 0.0228 (1.00) | 0.417 (1.00)
Amp Peak 7(11q23 3) | 34 (19%) | 144 | 0.695 (1.00) | 0.0856 (1.00) | 0.185 (1.00) | 0.6 (1.00) | 0.39 (1.00) | 0.343 (1.00)
Amp Peak 8(12p13 32) | 30 (17%) | 148 | 0.954 (1.00) | 0.116 (1.00) | 0.157 (1.00) | 0.452 (1.00) | 0.546 (1.00) | 1 (1.00)
Amp Peak 11(Xp22 33) | 13 (7%) | 165 | 0.614 (1.00) | 0.964 (1.00) | 1 (1.00) | 0.631 (1.00) | 0.0111 (1.00) | 0.387 (1.00)
Amp Peak 12(Xp11 22) | 17 (10%) | 161 | 0.5 (1.00) | 0.474 (1.00) | 1 (1.00) | 0.836 (1.00) | 0.304 (1.00) | 0.0718 (1.00)
Amp Peak 13(Xq11 2) | 23 (13%) | 155 | 0.564 (1.00) | 0.672 (1.00) | 0.37 (1.00) | 0.715 (1.00) | 0.0673 (1.00) | 0.121 (1.00)
Del Peak 2(1q44) | 12 (7%) | 166 | 0.916 (1.00) | 0.08 (1.00) | 1 (1.00) | 0.913 (1.00) | 0.045 (1.00) | 0.775 (1.00)
Del Peak 3(2q37 3) | 29 (16%) | 149 | 0.628 (1.00) | 0.112 (1.00) | 1 (1.00) | 0.565 (1.00) | 0.225 (1.00) | 0.417 (1.00)
Del Peak 4(3p21 1) | 18 (10%) | 160 | 0.354 (1.00) | 0.0231 (1.00) | 0.806 (1.00) | 0.652 (1.00) | 0.519 (1.00) | 0.135 (1.00)
Del Peak 5(3q29) | 19 (11%) | 159 | 0.469 (1.00) | 0.777 (1.00) | 0.147 (1.00) | 0.0488 (1.00) | 0.133 (1.00) | 0.47 (1.00)
Del Peak 6(4q33) | 58 (33%) | 120 | 0.528 (1.00) | 0.862 (1.00) | 0.259 (1.00) | 0.568 (1.00) | 0.161 (1.00) | 0.632 (1.00)
Del Peak 7(4q35 2) | 59 (33%) | 119 | 0.474 (1.00) | 0.805 (1.00) | 0.2 (1.00) | 0.704 (1.00) | 0.111 (1.00) | 0.751 (1.00)
Del Peak 8(5q35 2) | 24 (13%) | 154 | 0.107 (1.00) | 0.445 (1.00) | 0.379 (1.00) | 0.339 (1.00) | 0.224 (1.00) | 0.0289 (1.00)
Del Peak 9(6p24 1) | 16 (9%) | 162 | 0.058 (1.00) | 0.48 (1.00) | 0.431 (1.00) | 0.735 (1.00) | 0.00403 (0.813) | 0.294 (1.00)
Del Peak 10(6q24 3) | 28 (16%) | 150 | 0.0253 (1.00) | 0.312 (1.00) | 0.412 (1.00) | 0.536 (1.00) | 0.0226 (1.00) | 0.00648 (1.00)
Del Peak 13(11p15 5) | 38 (21%) | 140 | 0.451 (1.00) | 0.145 (1.00) | 0.0963 (1.00) | 0.635 (1.00) | 0.0315 (1.00) | 0.271 (1.00)
Del Peak 14(12p13 1) | 14 (8%) | 164 | 0.178 (1.00) | 0.967 (1.00) | 0.4 (1.00) | 0.727 (1.00) | 0.329 (1.00) | 0.264 (1.00)
Del Peak 15(13q14 2) | 58 (33%) | 120 | 0.472 (1.00) | 0.905 (1.00) | 0.629 (1.00) | 0.0641 (1.00) | 0.127 (1.00) | 0.15 (1.00)
Del Peak 16(13q34) | 43 (24%) | 135 | 0.327 (1.00) | 0.544 (1.00) | 0.38 (1.00) | 0.404 (1.00) | 0.63 (1.00) | 0.114 (1.00)
Del Peak 18(17q25 3) | 10 (6%) | 168 | 0.565 (1.00) | 0.586 (1.00) | 1 (1.00) | 0.721 (1.00) | 0.773 (1.00) | 0.755 (1.00)
Del Peak 19(18q23) | 30 (17%) | 148 | 0.64 (1.00) | 0.2 (1.00) | 0.688 (1.00) | 0.882 (1.00) | 0.935 (1.00) | 0.16 (1.00)
Del Peak 21(22q13 31) | 28 (16%) | 150 | 0.152 (1.00) | 0.406 (1.00) | 0.412 (1.00) | 0.711 (1.00) | 0.00606 (1.00) | 1 (1.00)
Del Peak 22(Xp22 31) | 44 (25%) | 134 | 0.675 (1.00) | 0.849 (1.00) | 0.484 (1.00) | 0.643 (1.00) | 0.879 (1.00) | 0.488 (1.00)
Del Peak 23(Xq21 1) | 29 (16%) | 149 | 0.678 (1.00) | 0.235 (1.00) | 0.543 (1.00) | 0.978 (1.00) | 0.176 (1.00) | 0.546 (1.00)

'Amp Peak 1(1q32.1) mutation analysis' versus 'AGE'

P value = 0.000363 (t-test), Q value = 0.075

Table S1. Gene #1: 'Amp Peak 1(1q32.1) mutation analysis' versus Clinical Feature #2: 'AGE'

| nPatients | Mean (Std.Dev)
--- | --- | ---
ALL | 178 | 43.1 (13.4)
AMP PEAK 1(1Q32.1) MUTATED | 21 | 53.2 (11.9)
AMP PEAK 1(1Q32.1) WILD-TYPE | 157 | 41.8 (13.0)

Figure S1. Get High-res Image Gene #1: 'Amp Peak 1(1q32.1) mutation analysis' versus Clinical Feature #2: 'AGE'

'Amp Peak 4(7q32.3) mutation analysis' versus 'AGE'

P value = 0.000236 (t-test), Q value = 0.049

Table S2. Gene #4: 'Amp Peak 4(7q32.3) mutation analysis' versus Clinical Feature #2: 'AGE'

| nPatients | Mean (Std.Dev)
--- | --- | ---
ALL | 178 | 43.1 (13.4)
AMP PEAK 4(7Q32.3) MUTATED | 65 | 48.0 (13.1)
AMP PEAK 4(7Q32.3) WILD-TYPE | 113 | 40.4 (12.8)

Figure S2. Get High-res Image Gene #4: 'Amp Peak 4(7q32.3) mutation analysis' versus Clinical Feature #2: 'AGE'

'Amp Peak 9(12q14.1) mutation analysis' versus 'Time to Death'

P value = 2.7e-05 (logrank test), Q value = 0.0058

Table S3. Gene #9: 'Amp Peak 9(12q14.1) mutation analysis' versus Clinical Feature #1: 'Time to Death'

| nPatients | nDeath | Duration Range (Median), Month
--- | --- | --- | ---
ALL | 177 | 50 | 0.0 - 211.2 (14.7)
AMP PEAK 9(12Q14.1) MUTATED | 13 | 9 | 1.2 - 80.0 (12.4)
AMP PEAK 9(12Q14.1) WILD-TYPE | 164 | 41 | 0.0 - 211.2 (14.9)

Figure S3. Get High-res Image Gene #9: 'Amp Peak 9(12q14.1) mutation analysis' versus Clinical Feature #1: 'Time to Death'

'Amp Peak 10(19q13.2) mutation analysis' versus 'Time to Death'

P value = 7.69e-05 (logrank test), Q value = 0.016

Table S4. Gene #10: 'Amp Peak 10(19q13.2) mutation analysis' versus Clinical Feature #1: 'Time to Death'

| nPatients | nDeath | Duration Range (Median), Month
--- | --- | --- | ---
ALL | 177 | 50 | 0.0 - 211.2 (14.7)
AMP PEAK 10(19Q13.2) MUTATED | 12 | 6 | 0.0 - 43.9 (12.8)
AMP PEAK 10(19Q13.2) WILD-TYPE | 165 | 44 | 0.1 - 211.2 (14.7)

Figure S4. Get High-res Image Gene #10: 'Amp Peak 10(19q13.2) mutation analysis' versus Clinical Feature #1: 'Time to Death'

'Del Peak 1(1p36.31) mutation analysis' versus 'AGE'

P value = 0.000459 (t-test), Q value = 0.094

Table S5. Gene #14: 'Del Peak 1(1p36.31) mutation analysis' versus Clinical Feature #2: 'AGE'

| nPatients | Mean (Std.Dev)
--- | --- | ---
ALL | 178 | 43.1 (13.4)
DEL PEAK 1(1P36.31) MUTATED | 69 | 47.5 (12.6)
DEL PEAK 1(1P36.31) WILD-TYPE | 109 | 40.4 (13.2)

Figure S5. Get High-res Image Gene #14: 'Del Peak 1(1p36.31) mutation analysis' versus Clinical Feature #2: 'AGE'

'Del Peak 1(1p36.31) mutation analysis' versus 'HISTOLOGICAL.TYPE'

P value = 3.16e-10 (Fisher's exact test), Q value = 6.8e-08

Table S6. Gene #14: 'Del Peak 1(1p36.31) mutation analysis' versus Clinical Feature #5: 'HISTOLOGICAL.TYPE'

nPatients | ASTROCYTOMA | OLIGOASTROCYTOMA | OLIGODENDROGLIOMA
--- | --- | --- | ---
ALL | 55 | 47 | 75
DEL PEAK 1(1P36.31) MUTATED | 8 | 11 | 50
DEL PEAK 1(1P36.31) WILD-TYPE | 47 | 36 | 25

Figure S6. Get High-res Image Gene #14: 'Del Peak 1(1p36.31) mutation analysis' versus Clinical Feature #5: 'HISTOLOGICAL.TYPE'

'Del Peak 1(1p36.31) mutation analysis' versus 'RADIATIONS.RADIATION.REGIMENINDICATION'

P value = 0.000673 (Fisher's exact test), Q value = 0.14

Table S7. Gene #14: 'Del Peak 1(1p36.31) mutation analysis' versus Clinical Feature #6: 'RADIATIONS.RADIATION.REGIMENINDICATION'

nPatients | NO | YES
--- | --- | ---
ALL | 82 | 96
DEL PEAK 1(1P36.31) MUTATED | 43 | 26
DEL PEAK 1(1P36.31) WILD-TYPE | 39 | 70

Figure S7. Get High-res Image Gene #14: 'Del Peak 1(1p36.31) mutation analysis' versus Clinical Feature #6: 'RADIATIONS.RADIATION.REGIMENINDICATION'

'Del Peak 11(9p21.3) mutation analysis' versus 'Time to Death'

P value = 5.14e-05 (logrank test), Q value = 0.011

Table S8. Gene #24: 'Del Peak 11(9p21.3) mutation analysis' versus Clinical Feature #1: 'Time to Death'

| nPatients | nDeath | Duration Range (Median), Month
--- | --- | --- | ---
ALL | 177 | 50 | 0.0 - 211.2 (14.7)
DEL PEAK 11(9P21.3) MUTATED | 65 | 26 | 0.1 - 117.4 (16.8)
DEL PEAK 11(9P21.3) WILD-TYPE | 112 | 24 | 0.0 - 211.2 (14.5)

Figure S8. Get High-res Image Gene #24: 'Del Peak 11(9p21.3) mutation analysis' versus Clinical Feature #1: 'Time to Death'

'Del Peak 11(9p21.3) mutation analysis' versus 'AGE'

P value = 0.000171 (t-test), Q value = 0.036

Table S9. Gene #24: 'Del Peak 11(9p21.3) mutation analysis' versus Clinical Feature #2: 'AGE'

| nPatients | Mean (Std.Dev)
--- | --- | ---
ALL | 178 | 43.1 (13.4)
DEL PEAK 11(9P21.3) MUTATED | 66 | 48.0 (13.0)
DEL PEAK 11(9P21.3) WILD-TYPE | 112 | 40.3 (12.8)

Figure S9. Get High-res Image Gene #24: 'Del Peak 11(9p21.3) mutation analysis' versus Clinical Feature #2: 'AGE'

'Del Peak 11(9p21.3) mutation analysis' versus 'RADIATIONS.RADIATION.REGIMENINDICATION'

P value = 4.37e-05 (Fisher's exact test), Q value = 0.0093

Table S10. Gene #24: 'Del Peak 11(9p21.3) mutation analysis' versus Clinical Feature #6: 'RADIATIONS.RADIATION.REGIMENINDICATION'

nPatients | NO | YES
--- | --- | ---
ALL | 82 | 96
DEL PEAK 11(9P21.3) MUTATED | 17 | 49
DEL PEAK 11(9P21.3) WILD-TYPE | 65 | 47

Figure S10. Get High-res Image Gene #24: 'Del Peak 11(9p21.3) mutation analysis' versus Clinical Feature #6: 'RADIATIONS.RADIATION.REGIMENINDICATION'

'Del Peak 12(10q26.2) mutation analysis' versus 'Time to Death'

P value = 0.000139 (logrank test), Q value = 0.029

Table S11. Gene #25: 'Del Peak 12(10q26.2) mutation analysis' versus Clinical Feature #1: 'Time to Death'

| nPatients | nDeath | Duration Range (Median), Month
--- | --- | --- | ---
ALL | 177 | 50 | 0.0 - 211.2 (14.7)
DEL PEAK 12(10Q26.2) MUTATED | 56 | 29 | 0.1 - 156.2 (15.8)
DEL PEAK 12(10Q26.2) WILD-TYPE | 121 | 21 | 0.0 - 211.2 (14.5)

Figure S11. Get High-res Image Gene #25: 'Del Peak 12(10q26.2) mutation analysis' versus Clinical Feature #1: 'Time to Death'

'Del Peak 17(14q24.3) mutation analysis' versus 'Time to Death'

P value = 0.000758 (logrank test), Q value = 0.15

Table S12. Gene #30: 'Del Peak 17(14q24.3) mutation analysis' versus Clinical Feature #1: 'Time to Death'

| nPatients | nDeath | Duration Range (Median), Month
--- | --- | --- | ---
ALL | 177 | 50 | 0.0 - 211.2 (14.7)
DEL PEAK 17(14Q24.3) MUTATED | 45 | 22 | 0.2 - 130.8 (17.3)
DEL PEAK 17(14Q24.3) WILD-TYPE | 132 | 28 | 0.0 - 211.2 (14.5)

Figure S12. Get High-res Image Gene #30: 'Del Peak 17(14q24.3) mutation analysis' versus Clinical Feature #1: 'Time to Death'

'Del Peak 20(19q13.42) mutation analysis' versus 'HISTOLOGICAL.TYPE'

P value = 1.86e-06 (Fisher's exact test), Q value = 4e-04

Table S13. Gene #33: 'Del Peak 20(19q13.42) mutation analysis' versus Clinical Feature #5: 'HISTOLOGICAL.TYPE'

nPatients | ASTROCYTOMA | OLIGOASTROCYTOMA | OLIGODENDROGLIOMA
--- | --- | --- | ---
ALL | 55 | 47 | 75
DEL PEAK 20(19Q13.42) MUTATED | 19 | 22 | 58
DEL PEAK 20(19Q13.42) WILD-TYPE | 36 | 25 | 17

Figure S13. Get High-res Image Gene #33: 'Del Peak 20(19q13.42) mutation analysis' versus Clinical Feature #5: 'HISTOLOGICAL.TYPE'

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.

- Clinical data file = LGG-TP.clin.merged.picked.txt

- Number of patients = 178

- Number of copy number variation regions = 36

- Number of selected clinical features = 6

- Exclude regions that fewer than K tumors have alterations, K = 3

Survival analysis

For survival clinical features, the Kaplan-Meier survival curves of tumors with and without gene cnvs were plotted and the statistical significance P values were estimated by logrank test (Bland and Altman 2004) using the 'survdiff' function in R

Student's t-test analysis

For continuous numerical clinical features, two-tailed Student's t test with unequal variance (Lehmann and Romano 2005) was applied to compare the clinical values between tumors with and without gene cnvs using 't.test' 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

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] Bland and Altman, Statistics notes: The logrank test, BMJ 328(7447):1073 (2004)
[2] Lehmann and Romano, Testing Statistical Hypotheses (3E ed.), New York: Springer. ISBN 0387988645 (2005)
[3] 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)
[4] 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)
[5] GISTIC_version2
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