Correlation between copy number variation genes (focal events) and selected clinical features
Kidney Renal Papillary Cell Carcinoma (Primary solid tumor)
15 January 2014 | analyses__2014_01_15
Maintainer Information
Citation Information
doi:10.7908/C1BZ64G1
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 selected clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C1BZ64G1
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 25 focal events and 11 clinical features across 139 patients, 13 significant findings detected with Q value < 0.25.

- amp_17q25.2 cnv correlated to 'PATHOLOGY.M.STAGE'.

- del_3p22.1 cnv correlated to 'NEOPLASM.DISEASESTAGE' and 'PATHOLOGY.T.STAGE'.

- del_6q27 cnv correlated to 'PATHOLOGY.T.STAGE'.

- del_9p21.3 cnv correlated to 'Time to Death', 'NEOPLASM.DISEASESTAGE', and 'PATHOLOGY.T.STAGE'.

- del_11q22.3 cnv correlated to 'Time to Death'.

- del_11q24.2 cnv correlated to 'Time to Death'.

- del_15q21.1 cnv correlated to 'Time to Death' and 'PATHOLOGY.T.STAGE'.

- del_16q24.1 cnv correlated to 'Time to Death'.

- del_xq28 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 25 focal events and 11 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 | NEOPLASM DISEASESTAGE | PATHOLOGY T STAGE | PATHOLOGY N STAGE | PATHOLOGY M STAGE | GENDER | KARNOFSKY PERFORMANCE SCORE | HISTOLOGICAL TYPE | NUMBERPACKYEARSSMOKED | YEAROFTOBACCOSMOKINGONSET
| nCNV (%) | nWild-Type | logrank test | t-test | Fisher's exact test | Fisher's exact test | Fisher's exact test | Fisher's exact test | Fisher's exact test | t-test | Fisher's exact test | t-test | t-test
del 9p21 3 | 21 (15%) | 118 | 0.000748 (0.158) | 0.304 (1.00) | 1.14e-05 (0.00252) | 1.92e-05 (0.00423) | 0.0364 (1.00) | 0.00604 (1.00) | 0.00814 (1.00) | 0.37 (1.00) | 1 (1.00) |  |
del 3p22 1 | 12 (9%) | 127 | 0.018 (1.00) | 0.118 (1.00) | 0.000233 (0.05) | 0.000222 (0.048) | 0.646 (1.00) | 0.0746 (1.00) | 0.754 (1.00) | 0.724 (1.00) | 0.424 (1.00) |  |
del 15q21 1 | 18 (13%) | 121 | 0.00042 (0.0899) | 0.0528 (1.00) | 0.00243 (0.493) | 0.00109 (0.229) | 0.0112 (1.00) | 0.0407 (1.00) | 0.416 (1.00) | 0.336 (1.00) | 1 (1.00) |  |
amp 17q25 2 | 100 (72%) | 39 | 0.555 (1.00) | 0.189 (1.00) | 0.525 (1.00) | 0.41 (1.00) | 0.883 (1.00) | 0.000745 (0.158) | 0.0139 (1.00) | 0.651 (1.00) | 0.185 (1.00) |  |
del 6q27 | 15 (11%) | 124 | 0.0677 (1.00) | 0.802 (1.00) | 0.00854 (1.00) | 0.000614 (0.131) | 0.267 (1.00) | 0.518 (1.00) | 0.0145 (1.00) | 0.397 (1.00) | 1 (1.00) |  |
del 11q22 3 | 15 (11%) | 124 | 6.73e-05 (0.0147) | 0.0313 (1.00) | 0.00142 (0.292) | 0.00133 (0.278) | 0.0585 (1.00) | 0.154 (1.00) | 0.385 (1.00) | 0.341 (1.00) | 0.503 (1.00) |  |
del 11q24 2 | 15 (11%) | 124 | 2.65e-05 (0.0058) | 0.0127 (1.00) | 0.00142 (0.292) | 0.00133 (0.278) | 0.133 (1.00) | 0.154 (1.00) | 0.772 (1.00) | 0.341 (1.00) | 0.503 (1.00) |  |
del 16q24 1 | 6 (4%) | 133 | 3.09e-07 (6.86e-05) | 0.985 (1.00) | 0.102 (1.00) | 0.12 (1.00) | 0.171 (1.00) | 0.337 (1.00) | 0.0678 (1.00) |  | 1 (1.00) |  |
del xq28 | 13 (9%) | 126 | 0.000175 (0.0379) | 0.187 (1.00) | 0.112 (1.00) | 0.13 (1.00) | 0.285 (1.00) | 0.57 (1.00) | 0.0625 (1.00) | 0.478 (1.00) | 1 (1.00) |  |
amp 2q32 1 | 32 (23%) | 107 | 0.259 (1.00) | 0.85 (1.00) | 0.033 (1.00) | 0.0821 (1.00) | 0.344 (1.00) | 0.0168 (1.00) | 0.38 (1.00) | 0.35 (1.00) | 0.621 (1.00) |  |
amp 3q22 3 | 47 (34%) | 92 | 0.264 (1.00) | 0.428 (1.00) | 0.262 (1.00) | 0.0604 (1.00) | 0.571 (1.00) | 0.353 (1.00) | 0.245 (1.00) | 0.225 (1.00) | 1 (1.00) | 0.379 (1.00) |
amp 7q22 1 | 83 (60%) | 56 | 0.0758 (1.00) | 0.498 (1.00) | 0.0033 (0.667) | 0.0099 (1.00) | 1 (1.00) | 0.183 (1.00) | 0.136 (1.00) | 0.189 (1.00) | 0.401 (1.00) |  |
amp 19p13 2 | 17 (12%) | 122 | 0.791 (1.00) | 0.0333 (1.00) | 0.885 (1.00) | 0.079 (1.00) | 0.812 (1.00) | 0.901 (1.00) | 1 (1.00) | 0.497 (1.00) | 0.55 (1.00) |  |
del 1p36 31 | 30 (22%) | 109 | 0.0385 (1.00) | 0.768 (1.00) | 0.00447 (0.893) | 0.002 (0.407) | 0.0531 (1.00) | 0.11 (1.00) | 0.261 (1.00) | 0.293 (1.00) | 1 (1.00) |  |
del 2q37 3 | 7 (5%) | 132 | 0.711 (1.00) | 0.175 (1.00) | 0.0434 (1.00) | 0.0222 (1.00) |  | 0.373 (1.00) | 0.198 (1.00) |  | 1 (1.00) |  |
del 4q32 1 | 15 (11%) | 124 | 0.255 (1.00) | 0.363 (1.00) | 0.0158 (1.00) | 0.0192 (1.00) | 0.0816 (1.00) | 0.0313 (1.00) | 0.149 (1.00) | 0.362 (1.00) | 1 (1.00) |  |
del 5p14 2 | 6 (4%) | 133 | 0.111 (1.00) | 0.331 (1.00) | 0.0426 (1.00) | 0.00446 (0.893) | 0.0172 (1.00) | 0.134 (1.00) | 0.366 (1.00) |  | 1 (1.00) |  |
del 5q35 2 | 8 (6%) | 131 | 0.769 (1.00) | 0.114 (1.00) | 0.0352 (1.00) | 0.00766 (1.00) | 0.102 (1.00) | 0.377 (1.00) | 0.243 (1.00) |  | 1 (1.00) |  |
del 6p12 3 | 13 (9%) | 126 | 0.0783 (1.00) | 0.721 (1.00) | 0.00806 (1.00) | 0.00544 (1.00) | 0.0453 (1.00) | 0.542 (1.00) | 0.532 (1.00) | 0.193 (1.00) | 1 (1.00) |  |
del 6q22 31 | 14 (10%) | 125 | 0.00675 (1.00) | 0.897 (1.00) | 0.0137 (1.00) | 0.00137 (0.284) | 0.179 (1.00) | 0.296 (1.00) | 0.0306 (1.00) | 0.363 (1.00) | 1 (1.00) |  |
del 14q11 2 | 30 (22%) | 109 | 0.105 (1.00) | 0.687 (1.00) | 0.0183 (1.00) | 0.0427 (1.00) | 0.14 (1.00) | 0.246 (1.00) | 0.261 (1.00) | 0.423 (1.00) | 0.61 (1.00) |  |
del 19p13 3 | 13 (9%) | 126 | 0.0115 (1.00) | 0.867 (1.00) | 0.112 (1.00) | 0.0331 (1.00) | 0.441 (1.00) | 0.35 (1.00) | 1 (1.00) | 0.28 (1.00) | 1 (1.00) |  |
del 19q13 42 | 12 (9%) | 127 | 0.812 (1.00) | 0.617 (1.00) | 0.212 (1.00) | 0.0627 (1.00) | 0.587 (1.00) | 0.732 (1.00) | 0.754 (1.00) | 0.741 (1.00) | 1 (1.00) |  |
del 21q22 3 | 27 (19%) | 112 | 0.979 (1.00) | 0.695 (1.00) | 0.00817 (1.00) | 0.00686 (1.00) | 0.379 (1.00) | 0.136 (1.00) | 0.243 (1.00) | 0.891 (1.00) | 1 (1.00) | 0.408 (1.00) |
del xp11 22 | 14 (10%) | 125 | 0.00579 (1.00) | 0.556 (1.00) | 0.0261 (1.00) | 0.00364 (0.731) | 0.285 (1.00) | 0.63 (1.00) | 0.0306 (1.00) | 0.341 (1.00) | 0.478 (1.00) |  |

'amp_17q25.2' versus 'PATHOLOGY.M.STAGE'

P value = 0.000745 (Fisher's exact test), Q value = 0.16

Table S1. Gene #4: 'amp_17q25.2' versus Clinical Feature #6: 'PATHOLOGY.M.STAGE'

nPatients | M0 | M1 | MX
--- | --- | --- | ---
ALL | 58 | 6 | 62
AMP PEAK 4(17Q25.2) MUTATED | 32 | 4 | 53
AMP PEAK 4(17Q25.2) WILD-TYPE | 26 | 2 | 9

Figure S1. Get High-res Image Gene #4: 'amp_17q25.2' versus Clinical Feature #6: 'PATHOLOGY.M.STAGE'

'del_3p22.1' versus 'NEOPLASM.DISEASESTAGE'

P value = 0.000233 (Fisher's exact test), Q value = 0.05

Table S2. Gene #8: 'del_3p22.1' versus Clinical Feature #3: 'NEOPLASM.DISEASESTAGE'

nPatients | STAGE I | STAGE II | STAGE III | STAGE IV
--- | --- | --- | --- | ---
ALL | 77 | 11 | 31 | 10
DEL PEAK 3(3P22.1) MUTATED | 1 | 1 | 7 | 3
DEL PEAK 3(3P22.1) WILD-TYPE | 76 | 10 | 24 | 7

Figure S2. Get High-res Image Gene #8: 'del_3p22.1' versus Clinical Feature #3: 'NEOPLASM.DISEASESTAGE'

'del_3p22.1' versus 'PATHOLOGY.T.STAGE'

P value = 0.000222 (Fisher's exact test), Q value = 0.048

Table S3. Gene #8: 'del_3p22.1' versus Clinical Feature #4: 'PATHOLOGY.T.STAGE'

nPatients | T1 | T2 | T3+T4
--- | --- | --- | ---
ALL | 82 | 17 | 40
DEL PEAK 3(3P22.1) MUTATED | 1 | 2 | 9
DEL PEAK 3(3P22.1) WILD-TYPE | 81 | 15 | 31

Figure S3. Get High-res Image Gene #8: 'del_3p22.1' versus Clinical Feature #4: 'PATHOLOGY.T.STAGE'

'del_6q27' versus 'PATHOLOGY.T.STAGE'

P value = 0.000614 (Fisher's exact test), Q value = 0.13

Table S4. Gene #14: 'del_6q27' versus Clinical Feature #4: 'PATHOLOGY.T.STAGE'

nPatients | T1 | T2 | T3+T4
--- | --- | --- | ---
ALL | 82 | 17 | 40
DEL PEAK 9(6Q27) MUTATED | 4 | 0 | 11
DEL PEAK 9(6Q27) WILD-TYPE | 78 | 17 | 29

Figure S4. Get High-res Image Gene #14: 'del_6q27' versus Clinical Feature #4: 'PATHOLOGY.T.STAGE'

'del_9p21.3' versus 'Time to Death'

P value = 0.000748 (logrank test), Q value = 0.16

Table S5. Gene #15: 'del_9p21.3' versus Clinical Feature #1: 'Time to Death'

| nPatients | nDeath | Duration Range (Median), Month
--- | --- | --- | ---
ALL | 127 | 15 | 0.0 - 194.8 (14.6)
DEL PEAK 10(9P21.3) MUTATED | 19 | 6 | 0.7 - 93.3 (11.1)
DEL PEAK 10(9P21.3) WILD-TYPE | 108 | 9 | 0.0 - 194.8 (15.5)

Figure S5. Get High-res Image Gene #15: 'del_9p21.3' versus Clinical Feature #1: 'Time to Death'

'del_9p21.3' versus 'NEOPLASM.DISEASESTAGE'

P value = 1.14e-05 (Fisher's exact test), Q value = 0.0025

Table S6. Gene #15: 'del_9p21.3' versus Clinical Feature #3: 'NEOPLASM.DISEASESTAGE'

nPatients | STAGE I | STAGE II | STAGE III | STAGE IV
--- | --- | --- | --- | ---
ALL | 77 | 11 | 31 | 10
DEL PEAK 10(9P21.3) MUTATED | 4 | 0 | 9 | 6
DEL PEAK 10(9P21.3) WILD-TYPE | 73 | 11 | 22 | 4

Figure S6. Get High-res Image Gene #15: 'del_9p21.3' versus Clinical Feature #3: 'NEOPLASM.DISEASESTAGE'

'del_9p21.3' versus 'PATHOLOGY.T.STAGE'

P value = 1.92e-05 (Fisher's exact test), Q value = 0.0042

Table S7. Gene #15: 'del_9p21.3' versus Clinical Feature #4: 'PATHOLOGY.T.STAGE'

nPatients | T1 | T2 | T3+T4
--- | --- | --- | ---
ALL | 82 | 17 | 40
DEL PEAK 10(9P21.3) MUTATED | 4 | 2 | 15
DEL PEAK 10(9P21.3) WILD-TYPE | 78 | 15 | 25

Figure S7. Get High-res Image Gene #15: 'del_9p21.3' versus Clinical Feature #4: 'PATHOLOGY.T.STAGE'

'del_11q22.3' versus 'Time to Death'

P value = 6.73e-05 (logrank test), Q value = 0.015

Table S8. Gene #16: 'del_11q22.3' versus Clinical Feature #1: 'Time to Death'

| nPatients | nDeath | Duration Range (Median), Month
--- | --- | --- | ---
ALL | 127 | 15 | 0.0 - 194.8 (14.6)
DEL PEAK 11(11Q22.3) MUTATED | 14 | 5 | 2.0 - 123.6 (9.9)
DEL PEAK 11(11Q22.3) WILD-TYPE | 113 | 10 | 0.0 - 194.8 (15.1)

Figure S8. Get High-res Image Gene #16: 'del_11q22.3' versus Clinical Feature #1: 'Time to Death'

'del_11q24.2' versus 'Time to Death'

P value = 2.65e-05 (logrank test), Q value = 0.0058

Table S9. Gene #17: 'del_11q24.2' versus Clinical Feature #1: 'Time to Death'

| nPatients | nDeath | Duration Range (Median), Month
--- | --- | --- | ---
ALL | 127 | 15 | 0.0 - 194.8 (14.6)
DEL PEAK 12(11Q24.2) MUTATED | 14 | 6 | 2.0 - 123.6 (11.0)
DEL PEAK 12(11Q24.2) WILD-TYPE | 113 | 9 | 0.0 - 194.8 (14.6)

Figure S9. Get High-res Image Gene #17: 'del_11q24.2' versus Clinical Feature #1: 'Time to Death'

'del_15q21.1' versus 'Time to Death'

P value = 0.00042 (logrank test), Q value = 0.09

Table S10. Gene #19: 'del_15q21.1' versus Clinical Feature #1: 'Time to Death'

| nPatients | nDeath | Duration Range (Median), Month
--- | --- | --- | ---
ALL | 127 | 15 | 0.0 - 194.8 (14.6)
DEL PEAK 14(15Q21.1) MUTATED | 17 | 5 | 0.1 - 194.8 (10.1)
DEL PEAK 14(15Q21.1) WILD-TYPE | 110 | 10 | 0.0 - 129.9 (14.9)

Figure S10. Get High-res Image Gene #19: 'del_15q21.1' versus Clinical Feature #1: 'Time to Death'

'del_15q21.1' versus 'PATHOLOGY.T.STAGE'

P value = 0.00109 (Fisher's exact test), Q value = 0.23

Table S11. Gene #19: 'del_15q21.1' versus Clinical Feature #4: 'PATHOLOGY.T.STAGE'

nPatients | T1 | T2 | T3+T4
--- | --- | --- | ---
ALL | 82 | 17 | 40
DEL PEAK 14(15Q21.1) MUTATED | 5 | 1 | 12
DEL PEAK 14(15Q21.1) WILD-TYPE | 77 | 16 | 28

Figure S11. Get High-res Image Gene #19: 'del_15q21.1' versus Clinical Feature #4: 'PATHOLOGY.T.STAGE'

'del_16q24.1' versus 'Time to Death'

P value = 3.09e-07 (logrank test), Q value = 6.9e-05

Table S12. Gene #20: 'del_16q24.1' versus Clinical Feature #1: 'Time to Death'

| nPatients | nDeath | Duration Range (Median), Month
--- | --- | --- | ---
ALL | 127 | 15 | 0.0 - 194.8 (14.6)
DEL PEAK 15(16Q24.1) MUTATED | 5 | 3 | 0.7 - 21.6 (11.1)
DEL PEAK 15(16Q24.1) WILD-TYPE | 122 | 12 | 0.0 - 194.8 (14.9)

Figure S12. Get High-res Image Gene #20: 'del_16q24.1' versus Clinical Feature #1: 'Time to Death'

'del_xq28' versus 'Time to Death'

P value = 0.000175 (logrank test), Q value = 0.038

Table S13. Gene #25: 'del_xq28' versus Clinical Feature #1: 'Time to Death'

| nPatients | nDeath | Duration Range (Median), Month
--- | --- | --- | ---
ALL | 127 | 15 | 0.0 - 194.8 (14.6)
DEL PEAK 20(XQ28) MUTATED | 12 | 4 | 0.1 - 25.1 (12.8)
DEL PEAK 20(XQ28) WILD-TYPE | 115 | 11 | 0.0 - 194.8 (14.6)

Figure S13. Get High-res Image Gene #25: 'del_xq28' versus Clinical Feature #1: 'Time to Death'

Methods & Data
Input

- Copy number data file = transformed.cor.cli.txt

- Clinical data file = KIRP-TP.merged_data.txt

- Number of patients = 139

- Number of significantly focal cnvs = 25

- 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

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 mutations 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

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] 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)
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