Acute Myeloid Leukemia: Correlation between gene mutation status and selected clinical features

Maintained by TCGA GDAC Team (Broad Institute/Dana-Farber Cancer Institute/Harvard Medical School)

Overview

Introduction

This pipeline computes the correlation between significantly recurrent gene mutations and selected clinical features.

Summary

Testing the association between mutation status of 48 genes and 3 clinical features across 199 patients, 6 significant findings detected with Q value < 0.25.

DNMT3A mutation correlated to 'Time to Death'.
IDH2 mutation correlated to 'AGE'.
TP53 mutation correlated to 'Time to Death'.
ZAN mutation correlated to 'AGE'.
FLJ43860 mutation correlated to 'Time to Death'.
NINL mutation correlated to 'AGE'.

Results

Overview of the results

Table 1. Get Full Table Overview of the association between mutation status of 48 genes and 3 clinical features. Shown in the table are P values (Q values). Thresholded by Q value < 0.25, 6 significant findings detected.


		Clinical Features	Time to Death	AGE	GENDER
	nMutated (%)	nWild-Type	logrank test	t-test	Fisher's exact test
DNMT3A	50 (25%)	149	0.000611 (0.0795)	0.0569 (1.00)	0.192 (1.00)
IDH2	20 (10%)	179	0.629 (1.00)	2.17e-05 (0.00287)	0.814 (1.00)
TP53	11 (6%)	188	7.67e-06 (0.00102)	0.00316 (0.404)	0.233 (1.00)
ZAN	6 (3%)	193	0.263 (1.00)	0.00108 (0.139)	0.0951 (1.00)
FLJ43860	3 (2%)	196	0.000592 (0.0775)	0.756 (1.00)	0.252 (1.00)
NINL	3 (2%)	196	0.811 (1.00)	9.99e-09 (1.34e-06)	1 (1.00)
IDH1	20 (10%)	179	0.932 (1.00)	0.331 (1.00)	0.479 (1.00)
U2AF1	10 (5%)	189	0.459 (1.00)	0.00364 (0.462)	0.0228 (1.00)
KRAS	9 (5%)	190	0.587 (1.00)	0.453 (1.00)	0.306 (1.00)
TET2	15 (8%)	184	0.865 (1.00)	0.175 (1.00)	0.289 (1.00)
FLT3	52 (26%)	147	0.206 (1.00)	0.352 (1.00)	0.519 (1.00)
NPM1	47 (24%)	152	0.222 (1.00)	0.967 (1.00)	0.136 (1.00)
NRAS	18 (9%)	181	0.875 (1.00)	0.531 (1.00)	0.625 (1.00)
OR5H6	4 (2%)	195		0.0986 (1.00)	0.334 (1.00)
RUNX1	17 (9%)	182	0.233 (1.00)	0.108 (1.00)	0.802 (1.00)
WT1	13 (7%)	186	0.672 (1.00)	0.0301 (1.00)	1 (1.00)
KIT	7 (4%)	192	0.901 (1.00)	0.49 (1.00)	0.705 (1.00)
PHF6	6 (3%)	193	0.873 (1.00)	0.232 (1.00)	0.0323 (1.00)
AP3S1	3 (2%)	196	0.74 (1.00)	0.537 (1.00)	0.594 (1.00)
SCRN3	3 (2%)	196		0.0541 (1.00)	0.594 (1.00)
MPRIP	3 (2%)	196		0.65 (1.00)	1 (1.00)
CYP21A2	4 (2%)	195	0.0181 (1.00)	0.556 (1.00)	1 (1.00)
PTPN11	7 (4%)	192	0.37 (1.00)	0.673 (1.00)	1 (1.00)
ETV6	5 (3%)	194	0.472 (1.00)	0.276 (1.00)	0.378 (1.00)
NFKBIZ	3 (2%)	196		0.0353 (1.00)	0.0939 (1.00)
LILRA3	3 (2%)	196		0.875 (1.00)	0.594 (1.00)
C17ORF97	5 (3%)	194	0.629 (1.00)	0.406 (1.00)	0.378 (1.00)
MUC4	7 (4%)	192	0.149 (1.00)	0.497 (1.00)	1 (1.00)
SMC3	6 (3%)	193	0.177 (1.00)	0.589 (1.00)	0.415 (1.00)
NOTCH2NL	3 (2%)	196		0.804 (1.00)	0.252 (1.00)
FAM5C	5 (3%)	194	0.119 (1.00)	0.045 (1.00)	0.378 (1.00)
PRUNE2	6 (3%)	193	0.418 (1.00)	0.0919 (1.00)	0.00834 (1.00)
SMC1A	5 (3%)	194	0.474 (1.00)	0.0224 (1.00)	0.378 (1.00)
ZNF275	3 (2%)	196		0.0723 (1.00)	0.594 (1.00)
C5ORF25	3 (2%)	196	0.0889 (1.00)	0.194 (1.00)	0.0939 (1.00)
MAP3K4	4 (2%)	195	0.236 (1.00)	0.138 (1.00)	0.334 (1.00)
CSPG4	3 (2%)	196	0.179 (1.00)	0.569 (1.00)	0.594 (1.00)
TRIM48	3 (2%)	196		0.204 (1.00)	0.594 (1.00)
ASXL1	5 (3%)	194	0.193 (1.00)	0.0641 (1.00)	0.662 (1.00)
CSMD1	6 (3%)	193	0.384 (1.00)	0.499 (1.00)	1 (1.00)
CPAMD8	3 (2%)	196		0.0723 (1.00)	0.594 (1.00)
PKD1L2	4 (2%)	195	0.00538 (0.678)	0.851 (1.00)	1 (1.00)
STAG2	4 (2%)	195	0.396 (1.00)	0.328 (1.00)	0.334 (1.00)
EZH2	3 (2%)	196		0.116 (1.00)	1 (1.00)
OR11H12	3 (2%)	196	0.531 (1.00)	0.376 (1.00)	0.594 (1.00)
ANKRD24	3 (2%)	196	0.178 (1.00)	0.757 (1.00)	1 (1.00)
CCDC74A	3 (2%)	196	0.526 (1.00)	0.349 (1.00)	0.252 (1.00)
QRICH2	4 (2%)	195	0.609 (1.00)	0.0273 (1.00)	1 (1.00)

'DNMT3A MUTATION STATUS' versus 'Time to Death'

P value = 0.000611 (logrank test), Q value = 0.079

Table S1. Gene #5: 'DNMT3A MUTATION STATUS' versus Clinical Feature #1: 'Time to Death'

	nPatients	nDeath	Duration Range (Median), Month
ALL	175	110	0.9 - 94.1 (12.0)
DNMT3A MUTATED	46	35	0.9 - 37.0 (9.0)
DNMT3A WILD-TYPE	129	75	0.9 - 94.1 (15.0)

Figure S1. Get High-res Image Gene #5: 'DNMT3A MUTATION STATUS' versus Clinical Feature #1: 'Time to Death'

'IDH2 MUTATION STATUS' versus 'AGE'

P value = 2.17e-05 (t-test), Q value = 0.0029

Table S2. Gene #7: 'IDH2 MUTATION STATUS' versus Clinical Feature #2: 'AGE'

	nPatients	Mean (Std.Dev)
ALL	199	55.0 (16.1)
IDH2 MUTATED	20	64.5 (8.0)
IDH2 WILD-TYPE	179	54.0 (16.4)

Figure S2. Get High-res Image Gene #7: 'IDH2 MUTATION STATUS' versus Clinical Feature #2: 'AGE'

'TP53 MUTATION STATUS' versus 'Time to Death'

P value = 7.67e-06 (logrank test), Q value = 0.001

Table S3. Gene #12: 'TP53 MUTATION STATUS' versus Clinical Feature #1: 'Time to Death'

	nPatients	nDeath	Duration Range (Median), Month
ALL	175	110	0.9 - 94.1 (12.0)
TP53 MUTATED	10	10	1.0 - 17.0 (6.0)
TP53 WILD-TYPE	165	100	0.9 - 94.1 (13.0)

Figure S3. Get High-res Image Gene #12: 'TP53 MUTATION STATUS' versus Clinical Feature #1: 'Time to Death'

'ZAN MUTATION STATUS' versus 'AGE'

P value = 0.00108 (t-test), Q value = 0.14

Table S4. Gene #40: 'ZAN MUTATION STATUS' versus Clinical Feature #2: 'AGE'

	nPatients	Mean (Std.Dev)
ALL	199	55.0 (16.1)
ZAN MUTATED	6	70.3 (6.7)
ZAN WILD-TYPE	193	54.5 (16.1)

Figure S4. Get High-res Image Gene #40: 'ZAN MUTATION STATUS' versus Clinical Feature #2: 'AGE'

'FLJ43860 MUTATION STATUS' versus 'Time to Death'

P value = 0.000592 (logrank test), Q value = 0.078

Table S5. Gene #46: 'FLJ43860 MUTATION STATUS' versus Clinical Feature #1: 'Time to Death'

	nPatients	nDeath	Duration Range (Median), Month
ALL	175	110	0.9 - 94.1 (12.0)
FLJ43860 MUTATED	3	3	1.0 - 9.0 (2.0)
FLJ43860 WILD-TYPE	172	107	0.9 - 94.1 (12.5)

Figure S5. Get High-res Image Gene #46: 'FLJ43860 MUTATION STATUS' versus Clinical Feature #1: 'Time to Death'

'NINL MUTATION STATUS' versus 'AGE'

P value = 9.99e-09 (t-test), Q value = 1.3e-06

Table S6. Gene #48: 'NINL MUTATION STATUS' versus Clinical Feature #2: 'AGE'

	nPatients	Mean (Std.Dev)
ALL	199	55.0 (16.1)
NINL MUTATED	3	44.7 (1.2)
NINL WILD-TYPE	196	55.2 (16.2)

Figure S6. Get High-res Image Gene #48: 'NINL MUTATION STATUS' versus Clinical Feature #2: 'AGE'

Methods & Data

Input

Mutation data file = LAML.mutsig.cluster.txt
Clinical data file = LAML.clin.merged.picked.txt
Number of patients = 199
Number of significantly mutated genes = 48
Number of selected clinical features = 3
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

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

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)

Made with Nozzle