Correlation between gene mutation status and selected clinical features

Kidney Renal Papillary Cell Carcinoma (Primary solid tumor)

28 January 2016 | analyses__2016_01_28

Maintainer Information

Citation Information

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 gene mutation status and selected clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C1V987G4

Overview

Introduction

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

Summary

Testing the association between mutation status of 26 genes and 12 clinical features across 282 patients, 2 significant findings detected with Q value < 0.25.

PBRM1 mutation correlated to 'Time to Death'.
CALCR mutation correlated to 'Time to Death'.

Results

Overview of the results

Table 1. Get Full Table Overview of the association between mutation status of 26 genes and 12 clinical features. Shown in the table are P values (Q values). Thresholded by Q value < 0.25, 2 significant findings detected.


		Clinical Features	Time to Death	YEARS TO BIRTH	PATHOLOGIC STAGE	PATHOLOGY T STAGE	PATHOLOGY N STAGE	PATHOLOGY M STAGE	GENDER	KARNOFSKY PERFORMANCE SCORE	NUMBER PACK YEARS SMOKED	YEAR OF TOBACCO SMOKING ONSET	RACE	ETHNICITY
	nMutated (%)	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	Wilcoxon-test	Wilcoxon-test	Wilcoxon-test	Fisher's exact test	Fisher's exact test
PBRM1	11 (4%)	271	0.000244 (0.0381)	0.0077 (0.382)	0.201 (1.00)	0.113 (1.00)	0.657 (1.00)	1 (1.00)	0.299 (1.00)		0.512 (1.00)		0.797 (1.00)	1 (1.00)
CALCR	3 (1%)	279	4.15e-06 (0.0013)	0.166 (1.00)	0.119 (1.00)	0.15 (1.00)	1 (1.00)	0.0874 (1.00)	1 (1.00)				1 (1.00)	0.129 (1.00)
SETD2	16 (6%)	266	0.0129 (0.382)	0.0793 (1.00)	0.00252 (0.262)	0.00431 (0.269)	0.431 (1.00)	0.144 (1.00)	0.57 (1.00)	0.499 (1.00)	0.834 (1.00)		0.412 (1.00)	1 (1.00)
NF2	10 (4%)	272	0.244 (1.00)	0.398 (1.00)	0.00384 (0.269)	0.00917 (0.382)	0.0355 (0.651)	0.31 (1.00)	0.467 (1.00)	0.977 (1.00)	0.454 (1.00)	0.882 (1.00)	0.565 (1.00)	1 (1.00)
ZNF814	9 (3%)	273	0.49 (1.00)	0.339 (1.00)	0.739 (1.00)	1 (1.00)			1 (1.00)		0.173 (1.00)		1 (1.00)	1 (1.00)
MET	21 (7%)	261	0.898 (1.00)	0.724 (1.00)	0.971 (1.00)	1 (1.00)	0.411 (1.00)	1 (1.00)	1 (1.00)	0.122 (1.00)	0.339 (1.00)	0.229 (1.00)	0.634 (1.00)	0.553 (1.00)
NEFH	6 (2%)	276	0.317 (1.00)	0.93 (1.00)	0.488 (1.00)	0.531 (1.00)		1 (1.00)	0.196 (1.00)				1 (1.00)	1 (1.00)
KRAS	5 (2%)	277	0.476 (1.00)	0.772 (1.00)	0.809 (1.00)	0.629 (1.00)		1 (1.00)	0.0197 (0.448)				0.0274 (0.535)	1 (1.00)
CUL3	10 (4%)	272	0.621 (1.00)	0.647 (1.00)	0.176 (1.00)	1 (1.00)	1 (1.00)	0.242 (1.00)	1 (1.00)		0.0135 (0.382)	0.256 (1.00)	1 (1.00)	1 (1.00)
PCF11	11 (4%)	271	0.985 (1.00)	0.332 (1.00)	1 (1.00)	0.698 (1.00)		1 (1.00)	1 (1.00)		0.621 (1.00)		0.619 (1.00)	0.342 (1.00)
BCLAF1	6 (2%)	276	0.842 (1.00)	0.562 (1.00)	0.137 (1.00)	0.0979 (1.00)	0.262 (1.00)	0.242 (1.00)	1 (1.00)				0.451 (1.00)	1 (1.00)
PAM	3 (1%)	279	0.423 (1.00)	0.562 (1.00)	0.257 (1.00)	0.694 (1.00)		1 (1.00)	0.566 (1.00)			0.481 (1.00)		1 (1.00)
SMARCB1	6 (2%)	276	0.26 (1.00)	0.295 (1.00)	0.0408 (0.67)	0.0459 (0.717)	1 (1.00)	1 (1.00)	1 (1.00)				1 (1.00)	1 (1.00)
KDM6A	10 (4%)	272	0.711 (1.00)	0.0122 (0.382)	0.74 (1.00)	1 (1.00)	0.546 (1.00)	1 (1.00)	1 (1.00)	0.698 (1.00)	0.181 (1.00)		0.181 (1.00)	1 (1.00)
AR	13 (5%)	269	0.969 (1.00)	0.43 (1.00)	0.438 (1.00)	0.426 (1.00)	1 (1.00)	1 (1.00)	0.346 (1.00)	0.397 (1.00)	0.944 (1.00)	0.977 (1.00)	0.54 (1.00)	1 (1.00)
TP53	7 (2%)	275	0.0119 (0.382)	0.134 (1.00)	0.0215 (0.448)	0.0619 (0.877)	1 (1.00)	0.0595 (0.877)	0.679 (1.00)				0.479 (1.00)	1 (1.00)
KRTAP4-5	5 (2%)	277	0.325 (1.00)	0.453 (1.00)	0.379 (1.00)	0.0207 (0.448)		1 (1.00)	0.328 (1.00)				0.209 (1.00)	1 (1.00)
BRAF	4 (1%)	278	0.296 (1.00)	0.983 (1.00)	0.706 (1.00)	1 (1.00)		1 (1.00)	1 (1.00)				0.626 (1.00)	1 (1.00)
KIAA0922	5 (2%)	277	0.841 (1.00)	0.253 (1.00)	0.809 (1.00)	0.633 (1.00)		1 (1.00)	0.328 (1.00)				0.627 (1.00)	1 (1.00)
KRT2	5 (2%)	277	0.362 (1.00)	0.0903 (1.00)	1 (1.00)	1 (1.00)		1 (1.00)	1 (1.00)		0.592 (1.00)	0.299 (1.00)	0.148 (1.00)	1 (1.00)
ALMS1	8 (3%)	274	0.618 (1.00)	0.37 (1.00)	0.738 (1.00)	1 (1.00)		1 (1.00)	0.113 (1.00)				0.231 (1.00)	0.277 (1.00)
GXYLT1	4 (1%)	278	0.574 (1.00)	0.258 (1.00)	0.769 (1.00)	0.739 (1.00)			1 (1.00)				0.626 (1.00)	1 (1.00)
ATP1B1	7 (2%)	275	0.989 (1.00)	0.583 (1.00)	0.69 (1.00)	0.584 (1.00)		1 (1.00)	0.0873 (1.00)				0.354 (1.00)	0.242 (1.00)
PTEN	7 (2%)	275	0.271 (1.00)	0.04 (0.67)	0.509 (1.00)	0.47 (1.00)	0.546 (1.00)	1 (1.00)	0.0168 (0.436)				0.481 (1.00)	1 (1.00)
SAV1	6 (2%)	276	0.869 (1.00)	0.682 (1.00)	0.325 (1.00)	1 (1.00)		1 (1.00)	0.348 (1.00)	0.228 (1.00)			0.109 (1.00)	1 (1.00)
IGSF3	4 (1%)	278	0.455 (1.00)	0.245 (1.00)	1 (1.00)	1 (1.00)		1 (1.00)	0.577 (1.00)				0.311 (1.00)	1 (1.00)

'PBRM1 MUTATION STATUS' versus 'Time to Death'

P value = 0.000244 (logrank test), Q value = 0.038

Table S1. Gene #22: 'PBRM1 MUTATION STATUS' versus Clinical Feature #1: 'Time to Death'

	nPatients	nDeath	Duration Range (Median), Month
ALL	279	41	0.1 - 194.8 (25.2)
PBRM1 MUTATED	11	4	0.1 - 67.2 (12.3)
PBRM1 WILD-TYPE	268	37	0.1 - 194.8 (25.5)

Figure S1. Get High-res Image Gene #22: 'PBRM1 MUTATION STATUS' versus Clinical Feature #1: 'Time to Death'

'CALCR MUTATION STATUS' versus 'Time to Death'

P value = 4.15e-06 (logrank test), Q value = 0.0013

Table S2. Gene #25: 'CALCR MUTATION STATUS' versus Clinical Feature #1: 'Time to Death'

	nPatients	nDeath	Duration Range (Median), Month
ALL	279	41	0.1 - 194.8 (25.2)
CALCR MUTATED	3	2	10.8 - 16.0 (12.9)
CALCR WILD-TYPE	276	39	0.1 - 194.8 (25.3)

Figure S2. Get High-res Image Gene #25: 'CALCR MUTATION STATUS' versus Clinical Feature #1: 'Time to Death'

Methods & Data

Input

Mutation data file = sample_sig_gene_table.txt from Mutsig_2CV pipeline
Processed Mutation data file = /xchip/cga/gdac-prod/tcga-gdac/jobResults/GDAC_Correlate_Genomic_Events_Preprocess/KIRP-TP/22574643/transformed.cor.cli.txt
Clinical data file = /xchip/cga/gdac-prod/tcga-gdac/jobResults/Append_Data/KIRP-TP/22507257/KIRP-TP.merged_data.txt
Number of patients = 282
Number of significantly mutated genes = 26
Number of selected clinical features = 12
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.

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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