Correlation between copy number variation genes (focal events) and selected clinical features
Acute Myeloid Leukemia (Primary blood derived cancer - Peripheral blood)
02 April 2015 | analyses__2015_04_02
Maintainer Information
Citation Information
doi:10.7908/C14J0D51
Maintained by TCGA GDAC Team (Broad Institute/MD Anderson Cancer Center/Harvard Medical School)
Cite as Broad Institute TCGA Genome Data Analysis Center (2015): Correlation between copy number variation genes (focal events) and selected clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C14J0D51
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 20 focal events and 5 clinical features across 191 patients, 11 significant findings detected with Q value < 0.25.

- amp_1q43 cnv correlated to 'YEARS_TO_BIRTH'.

- amp_11q23.3 cnv correlated to 'YEARS_TO_BIRTH'.

- amp_21q22.2 cnv correlated to 'Time to Death' and 'YEARS_TO_BIRTH'.

- del_3p13 cnv correlated to 'Time to Death'.

- del_5q31.2 cnv correlated to 'Time to Death' and 'YEARS_TO_BIRTH'.

- del_12p13.2 cnv correlated to 'Time to Death'.

- del_17q11.2 cnv correlated to 'Time to Death'.

- del_18p11.21 cnv correlated to 'Time to Death'.

- del_20q13.13 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 20 focal events and 5 clinical features. Shown in the table are P values (Q values). Thresholded by Q value < 0.25, 11 significant findings detected.

|  | Clinical Features | Time to Death | YEARS TO BIRTH | GENDER | RACE | ETHNICITY
| nCNV (%) | nWild-Type | logrank test | Wilcoxon-test | Fisher's exact test | Fisher's exact test | Fisher's exact test
amp 21q22 2 | 14 (7%) | 177 | 0.00622 (0.19) | 0.0236 (0.215) | 0.0922 (0.464) | 0.384 (0.784) | 1 (1.00)
del 5q31 2 | 18 (9%) | 173 | 0.0179 (0.209) | 0.0108 (0.19) | 0.0464 (0.357) | 1 (1.00) | 1 (1.00)
amp 1q43 | 7 (4%) | 184 | 0.194 (0.613) | 0.0209 (0.209) | 1 (1.00) | 1 (1.00) | 1 (1.00)
amp 11q23 3 | 17 (9%) | 174 | 0.137 (0.527) | 0.0171 (0.209) | 0.45 (0.865) | 1 (1.00) | 0.249 (0.663)
del 3p13 | 8 (4%) | 183 | 0.000606 (0.0606) | 0.112 (0.485) | 0.295 (0.74) | 0.0958 (0.464) | 1 (1.00)
del 12p13 2 | 10 (5%) | 181 | 0.00127 (0.0636) | 0.367 (0.781) | 0.351 (0.781) | 1 (1.00) | 1 (1.00)
del 17q11 2 | 13 (7%) | 178 | 0.0103 (0.19) | 0.321 (0.764) | 0.775 (1.00) | 0.654 (1.00) | 1 (1.00)
del 18p11 21 | 9 (5%) | 182 | 0.0199 (0.209) | 0.427 (0.838) | 0.185 (0.613) | 0.555 (0.962) | 1 (1.00)
del 20q13 13 | 4 (2%) | 187 | 0.0114 (0.19) | 0.0674 (0.397) | 0.627 (1.00) | 0.299 (0.74) | 1 (1.00)
amp 1p33 | 7 (4%) | 184 | 0.202 (0.613) | 0.119 (0.497) | 1 (1.00) | 1 (1.00) | 1 (1.00)
amp 13q31 3 | 7 (4%) | 184 | 0.84 (1.00) | 0.0648 (0.397) | 1 (1.00) | 1 (1.00) | 1 (1.00)
amp 19p13 2 | 6 (3%) | 185 | 0.701 (1.00) | 0.793 (1.00) | 0.223 (0.655) | 1 (1.00) | 1 (1.00)
amp 20q11 21 | 3 (2%) | 188 | 0.184 (0.613) | 0.346 (0.781) | 0.252 (0.663) | 0.233 (0.663) | 1 (1.00)
del 7p12 1 | 16 (8%) | 175 | 0.166 (0.613) | 0.484 (0.914) | 0.604 (1.00) | 1 (1.00) | 1 (1.00)
del 7q34 | 24 (13%) | 167 | 0.102 (0.464) | 0.197 (0.613) | 0.512 (0.917) | 0.768 (1.00) | 1 (1.00)
del 7q34 | 24 (13%) | 167 | 0.102 (0.464) | 0.197 (0.613) | 0.512 (0.917) | 0.77 (1.00) | 1 (1.00)
del 9q21 32 | 5 (3%) | 186 | 0.735 (1.00) | 0.417 (0.834) | 0.378 (0.784) | 0.362 (0.781) | 1 (1.00)
del 12q21 33 | 3 (2%) | 188 | 0.367 (0.781) | 0.0366 (0.305) | 0.252 (0.663) | 1 (1.00) | 1 (1.00)
del 16q23 1 | 9 (5%) | 182 | 0.0992 (0.464) | 0.304 (0.74) | 0.513 (0.917) | 0.558 (0.962) | 1 (1.00)
del 17p13 2 | 15 (8%) | 176 | 0.0528 (0.377) | 0.129 (0.516) | 0.0565 (0.377) | 0.666 (1.00) | 1 (1.00)

'amp_1q43' versus 'YEARS_TO_BIRTH'

P value = 0.0209 (Wilcoxon-test), Q value = 0.21

Table S1. Gene #2: 'amp_1q43' versus Clinical Feature #2: 'YEARS_TO_BIRTH'

| nPatients | Mean (Std.Dev)
--- | --- | ---
ALL | 191 | 55.2 (16.1)
AMP PEAK 2(1Q43) MUTATED | 7 | 67.6 (11.3)
AMP PEAK 2(1Q43) WILD-TYPE | 184 | 54.8 (16.1)

Figure S1. Get High-res Image Gene #2: 'amp_1q43' versus Clinical Feature #2: 'YEARS_TO_BIRTH'

'amp_11q23.3' versus 'YEARS_TO_BIRTH'

P value = 0.0171 (Wilcoxon-test), Q value = 0.21

Table S2. Gene #3: 'amp_11q23.3' versus Clinical Feature #2: 'YEARS_TO_BIRTH'

| nPatients | Mean (Std.Dev)
--- | --- | ---
ALL | 191 | 55.2 (16.1)
AMP PEAK 3(11Q23.3) MUTATED | 17 | 63.3 (12.1)
AMP PEAK 3(11Q23.3) WILD-TYPE | 174 | 54.4 (16.2)

Figure S2. Get High-res Image Gene #3: 'amp_11q23.3' versus Clinical Feature #2: 'YEARS_TO_BIRTH'

'amp_21q22.2' versus 'Time to Death'

P value = 0.00622 (logrank test), Q value = 0.19

Table S3. Gene #7: 'amp_21q22.2' versus Clinical Feature #1: 'Time to Death'

| nPatients | nDeath | Duration Range (Median), Month
--- | --- | --- | ---
ALL | 178 | 116 | 0.0 - 94.1 (11.0)
AMP PEAK 7(21Q22.2) MUTATED | 12 | 10 | 1.0 - 24.0 (5.5)
AMP PEAK 7(21Q22.2) WILD-TYPE | 166 | 106 | 0.0 - 94.1 (12.0)

Figure S3. Get High-res Image Gene #7: 'amp_21q22.2' versus Clinical Feature #1: 'Time to Death'

'amp_21q22.2' versus 'YEARS_TO_BIRTH'

P value = 0.0236 (Wilcoxon-test), Q value = 0.21

Table S4. Gene #7: 'amp_21q22.2' versus Clinical Feature #2: 'YEARS_TO_BIRTH'

| nPatients | Mean (Std.Dev)
--- | --- | ---
ALL | 191 | 55.2 (16.1)
AMP PEAK 7(21Q22.2) MUTATED | 14 | 63.7 (16.7)
AMP PEAK 7(21Q22.2) WILD-TYPE | 177 | 54.6 (15.9)

Figure S4. Get High-res Image Gene #7: 'amp_21q22.2' versus Clinical Feature #2: 'YEARS_TO_BIRTH'

'del_3p13' versus 'Time to Death'

P value = 0.000606 (logrank test), Q value = 0.061

Table S5. Gene #8: 'del_3p13' versus Clinical Feature #1: 'Time to Death'

| nPatients | nDeath | Duration Range (Median), Month
--- | --- | --- | ---
ALL | 178 | 116 | 0.0 - 94.1 (11.0)
DEL PEAK 2(3P13) MUTATED | 8 | 7 | 0.0 - 14.0 (1.5)
DEL PEAK 2(3P13) WILD-TYPE | 170 | 109 | 0.0 - 94.1 (12.0)

Figure S5. Get High-res Image Gene #8: 'del_3p13' versus Clinical Feature #1: 'Time to Death'

'del_5q31.2' versus 'Time to Death'

P value = 0.0179 (logrank test), Q value = 0.21

Table S6. Gene #9: 'del_5q31.2' versus Clinical Feature #1: 'Time to Death'

| nPatients | nDeath | Duration Range (Median), Month
--- | --- | --- | ---
ALL | 178 | 116 | 0.0 - 94.1 (11.0)
DEL PEAK 3(5Q31.2) MUTATED | 17 | 15 | 1.0 - 73.0 (10.0)
DEL PEAK 3(5Q31.2) WILD-TYPE | 161 | 101 | 0.0 - 94.1 (12.0)

Figure S6. Get High-res Image Gene #9: 'del_5q31.2' versus Clinical Feature #1: 'Time to Death'

'del_5q31.2' versus 'YEARS_TO_BIRTH'

P value = 0.0108 (Wilcoxon-test), Q value = 0.19

Table S7. Gene #9: 'del_5q31.2' versus Clinical Feature #2: 'YEARS_TO_BIRTH'

| nPatients | Mean (Std.Dev)
--- | --- | ---
ALL | 191 | 55.2 (16.1)
DEL PEAK 3(5Q31.2) MUTATED | 18 | 64.3 (13.0)
DEL PEAK 3(5Q31.2) WILD-TYPE | 173 | 54.3 (16.1)

Figure S7. Get High-res Image Gene #9: 'del_5q31.2' versus Clinical Feature #2: 'YEARS_TO_BIRTH'

'del_12p13.2' versus 'Time to Death'

P value = 0.00127 (logrank test), Q value = 0.064

Table S8. Gene #14: 'del_12p13.2' versus Clinical Feature #1: 'Time to Death'

| nPatients | nDeath | Duration Range (Median), Month
--- | --- | --- | ---
ALL | 178 | 116 | 0.0 - 94.1 (11.0)
DEL PEAK 10(12P13.2) MUTATED | 9 | 9 | 0.0 - 22.1 (7.0)
DEL PEAK 10(12P13.2) WILD-TYPE | 169 | 107 | 0.0 - 94.1 (12.0)

Figure S8. Get High-res Image Gene #14: 'del_12p13.2' versus Clinical Feature #1: 'Time to Death'

'del_17q11.2' versus 'Time to Death'

P value = 0.0103 (logrank test), Q value = 0.19

Table S9. Gene #18: 'del_17q11.2' versus Clinical Feature #1: 'Time to Death'

| nPatients | nDeath | Duration Range (Median), Month
--- | --- | --- | ---
ALL | 178 | 116 | 0.0 - 94.1 (11.0)
DEL PEAK 14(17Q11.2) MUTATED | 12 | 11 | 0.0 - 49.0 (4.5)
DEL PEAK 14(17Q11.2) WILD-TYPE | 166 | 105 | 0.0 - 94.1 (11.5)

Figure S9. Get High-res Image Gene #18: 'del_17q11.2' versus Clinical Feature #1: 'Time to Death'

'del_18p11.21' versus 'Time to Death'

P value = 0.0199 (logrank test), Q value = 0.21

Table S10. Gene #19: 'del_18p11.21' versus Clinical Feature #1: 'Time to Death'

| nPatients | nDeath | Duration Range (Median), Month
--- | --- | --- | ---
ALL | 178 | 116 | 0.0 - 94.1 (11.0)
DEL PEAK 15(18P11.21) MUTATED | 8 | 8 | 1.0 - 17.0 (9.5)
DEL PEAK 15(18P11.21) WILD-TYPE | 170 | 108 | 0.0 - 94.1 (11.5)

Figure S10. Get High-res Image Gene #19: 'del_18p11.21' versus Clinical Feature #1: 'Time to Death'

'del_20q13.13' versus 'Time to Death'

P value = 0.0114 (logrank test), Q value = 0.19

Table S11. Gene #20: 'del_20q13.13' versus Clinical Feature #1: 'Time to Death'

| nPatients | nDeath | Duration Range (Median), Month
--- | --- | --- | ---
ALL | 178 | 116 | 0.0 - 94.1 (11.0)
DEL PEAK 16(20Q13.13) MUTATED | 4 | 4 | 0.0 - 10.0 (7.0)
DEL PEAK 16(20Q13.13) WILD-TYPE | 174 | 112 | 0.0 - 94.1 (12.0)

Figure S11. Get High-res Image Gene #20: 'del_20q13.13' 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/LAML-TB/15087095/transformed.cor.cli.txt

- Clinical data file = /xchip/cga/gdac-prod/tcga-gdac/jobResults/Append_Data/LAML-TB/15082450/LAML-TB.merged_data.txt

- Number of patients = 191

- Number of significantly focal cnvs = 20

- Number of selected clinical features = 5

- 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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