Breast Invasive Carcinoma: 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 100 genes and 5 clinical features across 507 patients, 2 significant findings detected with Q value < 0.25.

MAP3K1 mutation correlated to 'AGE'.
PYCRL mutation correlated to 'Time to Death'.

Results

Overview of the results

Table 1. Get Full Table Overview of the association between mutation status of 100 genes and 5 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	AGE	GENDER	RADIATIONS RADIATION REGIMENINDICATION	NEOADJUVANT THERAPY
	nMutated (%)	nWild-Type	logrank test	t-test	Fisher's exact test	Fisher's exact test	Fisher's exact test
MAP3K1	36 (7%)	471	0.643 (1.00)	5.69e-05 (0.0283)	1 (1.00)	0.246 (1.00)	0.861 (1.00)
PYCRL	3 (1%)	504	0 (0)	0.633 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)
PIK3CA	158 (31%)	349	0.858 (1.00)	0.0765 (1.00)	1 (1.00)	0.52 (1.00)	1 (1.00)
TP53	139 (27%)	368	0.786 (1.00)	0.498 (1.00)	0.195 (1.00)	0.435 (1.00)	0.544 (1.00)
GATA3	53 (10%)	454	0.608 (1.00)	0.0149 (1.00)	0.486 (1.00)	0.192 (1.00)	0.302 (1.00)
MLL3	29 (6%)	478	0.747 (1.00)	0.0219 (1.00)	1 (1.00)	0.831 (1.00)	0.332 (1.00)
CDH1	31 (6%)	476	0.904 (1.00)	0.096 (1.00)	1 (1.00)	1 (1.00)	0.852 (1.00)
MAP2K4	18 (4%)	489	0.103 (1.00)	0.0249 (1.00)	1 (1.00)	0.422 (1.00)	0.33 (1.00)
PIK3R1	14 (3%)	493	0.213 (1.00)	0.88 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)
PTEN	14 (3%)	493	0.241 (1.00)	0.392 (1.00)	1 (1.00)	1 (1.00)	0.787 (1.00)
RUNX1	14 (3%)	493	0.176 (1.00)	0.879 (1.00)	1 (1.00)	0.767 (1.00)	0.586 (1.00)
TBX3	11 (2%)	496	0.258 (1.00)	0.0523 (1.00)	1 (1.00)	0.735 (1.00)	0.538 (1.00)
AKT1	12 (2%)	495	0.223 (1.00)	0.548 (1.00)	1 (1.00)	0.194 (1.00)	0.769 (1.00)
CTCF	11 (2%)	496	0.162 (1.00)	0.777 (1.00)	1 (1.00)	1 (1.00)	0.375 (1.00)
NCOR1	15 (3%)	492	0.558 (1.00)	0.327 (1.00)	1 (1.00)	0.769 (1.00)	0.295 (1.00)
RPGR	10 (2%)	497	0.783 (1.00)	0.81 (1.00)	1 (1.00)	0.735 (1.00)	0.748 (1.00)
RB1	9 (2%)	498	0.69 (1.00)	0.305 (1.00)	1 (1.00)	0.455 (1.00)	0.318 (1.00)
CBFB	5 (1%)	502	0.867 (1.00)	0.14 (1.00)	1 (1.00)	1 (1.00)	0.409 (1.00)
ZFP36L1	6 (1%)	501	0.968 (1.00)	0.166 (1.00)	1 (1.00)	0.195 (1.00)	0.408 (1.00)
CDKN1B	5 (1%)	502	0.469 (1.00)	0.982 (1.00)	1 (1.00)	1 (1.00)	0.409 (1.00)
FOXA1	7 (1%)	500	0.0014 (0.695)	0.0231 (1.00)	1 (1.00)	1 (1.00)	0.705 (1.00)
PRRX1	5 (1%)	502	0.505 (1.00)	0.785 (1.00)	1 (1.00)	0.13 (1.00)	0.653 (1.00)
MUC4	13 (3%)	494	0.366 (1.00)	0.958 (1.00)	1 (1.00)	0.357 (1.00)	0.78 (1.00)
AFF2	11 (2%)	496	0.716 (1.00)	0.0188 (1.00)	1 (1.00)	0.503 (1.00)	1 (1.00)
DSPP	6 (1%)	501	0.242 (1.00)	0.155 (1.00)	1 (1.00)	0.668 (1.00)	1 (1.00)
ATN1	8 (2%)	499	0.235 (1.00)	0.72 (1.00)	1 (1.00)	0.456 (1.00)	0.479 (1.00)
MYB	7 (1%)	500	0.219 (1.00)	0.485 (1.00)	1 (1.00)	0.0935 (1.00)	0.456 (1.00)
DALRD3	6 (1%)	501	0.613 (1.00)	0.0641 (1.00)	1 (1.00)	0.353 (1.00)	0.696 (1.00)
GPS2	5 (1%)	502	0.269 (1.00)	0.668 (1.00)	1 (1.00)	0.618 (1.00)	1 (1.00)
FAM166A	4 (1%)	503	0.961 (1.00)	0.978 (1.00)	1 (1.00)	1 (1.00)	0.312 (1.00)
NKAIN4	3 (1%)	504	0.592 (1.00)	0.168 (1.00)	1 (1.00)	0.0203 (1.00)	0.572 (1.00)
PIWIL1	8 (2%)	499	0.189 (1.00)	0.718 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)
SF3B1	10 (2%)	497	0.386 (1.00)	0.378 (1.00)	1 (1.00)	1 (1.00)	0.534 (1.00)
SAAL1	5 (1%)	502	0.202 (1.00)	0.819 (1.00)	1 (1.00)	0.618 (1.00)	1 (1.00)
TMEM82	4 (1%)	503	1 (1.00)	0.269 (1.00)	1 (1.00)	0.579 (1.00)	0.146 (1.00)
HIST1H2BC	4 (1%)	503	0.556 (1.00)	0.657 (1.00)	1 (1.00)	1 (1.00)	0.312 (1.00)
TBL1XR1	5 (1%)	502	0.00337 (1.00)	0.257 (1.00)	1 (1.00)	1 (1.00)	0.409 (1.00)
WNT7A	5 (1%)	502	0.6 (1.00)	0.938 (1.00)	1 (1.00)	0.618 (1.00)	0.653 (1.00)
BID	4 (1%)	503	0.175 (1.00)	0.0368 (1.00)	1 (1.00)	0.303 (1.00)	0.312 (1.00)
LRFN4	4 (1%)	503	0.159 (1.00)	0.758 (1.00)	1 (1.00)	0.579 (1.00)	0.312 (1.00)
TLE6	6 (1%)	501	0.264 (1.00)	0.488 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)
FER1L5	7 (1%)	500	0.752 (1.00)	0.0217 (1.00)	1 (1.00)	0.399 (1.00)	0.0221 (1.00)
HIST1H1C	4 (1%)	503	0.766 (1.00)	0.979 (1.00)	0.0466 (1.00)	0.579 (1.00)	1 (1.00)
GPR32	5 (1%)	502	0.733 (1.00)	0.155 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)
MLLT4	7 (1%)	500	0.0724 (1.00)	0.306 (1.00)	1 (1.00)	0.68 (1.00)	0.705 (1.00)
ITPKB	7 (1%)	500	0.489 (1.00)	0.0247 (1.00)	1 (1.00)	0.198 (1.00)	1 (1.00)
COL18A1	6 (1%)	501	0.524 (1.00)	0.19 (1.00)	1 (1.00)	0.668 (1.00)	0.696 (1.00)
CCR2	4 (1%)	503	0.85 (1.00)	0.38 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)
HAUS5	6 (1%)	501	0.67 (1.00)	0.978 (1.00)	1 (1.00)	0.195 (1.00)	1 (1.00)
MUC5B	12 (2%)	495	0.0251 (1.00)	0.954 (1.00)	1 (1.00)	1 (1.00)	0.565 (1.00)
LLGL2	5 (1%)	502	0.445 (1.00)	0.036 (1.00)	1 (1.00)	0.618 (1.00)	1 (1.00)
CIRBP	3 (1%)	504	0.619 (1.00)	0.096 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)
GPRIN2	4 (1%)	503	0.208 (1.00)	0.26 (1.00)	1 (1.00)	1 (1.00)	0.312 (1.00)
KLRG2	3 (1%)	504		0.307 (1.00)	1 (1.00)	0.184 (1.00)	0.572 (1.00)
PQLC2	4 (1%)	503	0.283 (1.00)	0.0468 (1.00)	1 (1.00)	0.579 (1.00)	0.645 (1.00)
GLI4	3 (1%)	504	0.475 (1.00)	0.574 (1.00)	1 (1.00)	0.565 (1.00)	1 (1.00)
HLA-A	4 (1%)	503	0.21 (1.00)	0.449 (1.00)	1 (1.00)	0.303 (1.00)	1 (1.00)
UBC	6 (1%)	501	0.323 (1.00)	0.736 (1.00)	1 (1.00)	0.668 (1.00)	0.238 (1.00)
MYT1L	8 (2%)	499	0.888 (1.00)	0.736 (1.00)	1 (1.00)	0.224 (1.00)	0.723 (1.00)
PIP4K2C	5 (1%)	502	0.149 (1.00)	0.759 (1.00)	1 (1.00)	0.618 (1.00)	1 (1.00)
PPEF1	6 (1%)	501	0.53 (1.00)	0.588 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)
KCNQ2	4 (1%)	503	0.41 (1.00)	0.923 (1.00)	1 (1.00)	0.579 (1.00)	0.146 (1.00)
LYSMD3	4 (1%)	503	0.736 (1.00)	0.58 (1.00)	1 (1.00)	1 (1.00)	0.645 (1.00)
NF1	12 (2%)	495	0.518 (1.00)	0.646 (1.00)	1 (1.00)	0.194 (1.00)	0.769 (1.00)
ARID1A	8 (2%)	499	0.975 (1.00)	0.507 (1.00)	1 (1.00)	0.456 (1.00)	0.148 (1.00)
ATP10B	10 (2%)	497	0.65 (1.00)	0.286 (1.00)	1 (1.00)	0.735 (1.00)	1 (1.00)
GRIN2A	9 (2%)	498	0.32 (1.00)	0.733 (1.00)	1 (1.00)	0.455 (1.00)	0.318 (1.00)
MED23	8 (2%)	499	0.46 (1.00)	0.0213 (1.00)	1 (1.00)	0.69 (1.00)	0.723 (1.00)
FLG	16 (3%)	491	0.526 (1.00)	0.345 (1.00)	1 (1.00)	0.777 (1.00)	0.803 (1.00)
FMN2	7 (1%)	500	0.754 (1.00)	0.103 (1.00)	1 (1.00)	0.68 (1.00)	0.456 (1.00)
KIAA1644	3 (1%)	504	0.186 (1.00)	0.85 (1.00)	1 (1.00)	0.565 (1.00)	1 (1.00)
PRND	3 (1%)	504	0.737 (1.00)	0.785 (1.00)	1 (1.00)	1 (1.00)	0.572 (1.00)
SPTA1	12 (2%)	495	0.0458 (1.00)	0.342 (1.00)	1 (1.00)	0.194 (1.00)	0.375 (1.00)
CHST2	3 (1%)	504	0.647 (1.00)	0.452 (1.00)	1 (1.00)	0.0203 (1.00)	0.0705 (1.00)
RGS7	5 (1%)	502	0.694 (1.00)	0.71 (1.00)	1 (1.00)	0.618 (1.00)	0.653 (1.00)
CCDC146	5 (1%)	502	0.641 (1.00)	0.564 (1.00)	1 (1.00)	0.618 (1.00)	0.653 (1.00)
OPRM1	5 (1%)	502	0.492 (1.00)	0.276 (1.00)	1 (1.00)	1 (1.00)	0.409 (1.00)
PCDHA8	6 (1%)	501	0.00555 (1.00)	0.944 (1.00)	1 (1.00)	0.195 (1.00)	1 (1.00)
PIP5K1C	3 (1%)	504	0.683 (1.00)	0.487 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)
CCND3	3 (1%)	504	0.502 (1.00)	0.147 (1.00)	1 (1.00)	1 (1.00)	0.572 (1.00)
CCT6B	5 (1%)	502	0.167 (1.00)	1 (1.00)	0.058 (1.00)	1 (1.00)	1 (1.00)
OBSCN	17 (3%)	490	0.365 (1.00)	0.368 (1.00)	1 (1.00)	1 (1.00)	0.33 (1.00)
TPO	6 (1%)	501	0.406 (1.00)	0.187 (1.00)	1 (1.00)	0.668 (1.00)	1 (1.00)
SELL	4 (1%)	503	0.602 (1.00)	0.717 (1.00)	1 (1.00)	1 (1.00)	0.645 (1.00)
CCDC88B	5 (1%)	502	0.681 (1.00)	0.0829 (1.00)	1 (1.00)	0.13 (1.00)	0.653 (1.00)
SARM1	3 (1%)	504	0.57 (1.00)	0.771 (1.00)	1 (1.00)	0.565 (1.00)	1 (1.00)
SPEN	13 (3%)	494	0.0978 (1.00)	0.113 (1.00)	1 (1.00)	0.357 (1.00)	1 (1.00)
EPS8L1	4 (1%)	503	0.248 (1.00)	0.175 (1.00)	1 (1.00)	1 (1.00)	0.645 (1.00)
ZP4	5 (1%)	502	0.515 (1.00)	0.139 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)
C19ORF39	3 (1%)	504	0.216 (1.00)	0.106 (1.00)	1 (1.00)	1 (1.00)	0.572 (1.00)
CCDC159	3 (1%)	504	0.395 (1.00)	0.341 (1.00)	0.0352 (1.00)	0.565 (1.00)	1 (1.00)
H2BFWT	3 (1%)	504		0.589 (1.00)	1 (1.00)	1 (1.00)	0.572 (1.00)
PHLDA1	3 (1%)	504	0.945 (1.00)	0.451 (1.00)	1 (1.00)	0.565 (1.00)	1 (1.00)
MEFV	6 (1%)	501	0.545 (1.00)	0.0209 (1.00)	0.0693 (1.00)	1 (1.00)	0.408 (1.00)
NEK5	6 (1%)	501	0.507 (1.00)	0.0998 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)
KCNT2	8 (2%)	499	0.695 (1.00)	0.372 (1.00)	1 (1.00)	0.456 (1.00)	0.479 (1.00)
LIF	3 (1%)	504	0.557 (1.00)	0.555 (1.00)	1 (1.00)	0.565 (1.00)	1 (1.00)
PRAME	5 (1%)	502	0.763 (1.00)	0.756 (1.00)	1 (1.00)	0.618 (1.00)	1 (1.00)
C1ORF65	4 (1%)	503	0.176 (1.00)	0.91 (1.00)	1 (1.00)	0.303 (1.00)	1 (1.00)
LPO	5 (1%)	502	0.571 (1.00)	0.022 (1.00)	1 (1.00)	0.618 (1.00)	0.653 (1.00)

'MAP3K1 MUTATION STATUS' versus 'AGE'

P value = 5.69e-05 (t-test), Q value = 0.028

Table S1. Gene #4: 'MAP3K1 MUTATION STATUS' versus Clinical Feature #2: 'AGE'

	nPatients	Mean (Std.Dev)
ALL	507	57.8 (13.1)
MAP3K1 MUTATED	36	65.9 (11.2)
MAP3K1 WILD-TYPE	471	57.2 (13.1)

Figure S1. Get High-res Image Gene #4: 'MAP3K1 MUTATION STATUS' versus Clinical Feature #2: 'AGE'

'PYCRL MUTATION STATUS' versus 'Time to Death'

P value = 0 (logrank test), Q value = 0

Table S2. Gene #51: 'PYCRL MUTATION STATUS' versus Clinical Feature #1: 'Time to Death'

	nPatients	nDeath	Duration Range (Median), Month
ALL	476	64	0.1 - 223.4 (24.4)
PYCRL MUTATED	3	1	2.5 - 7.4 (5.8)
PYCRL WILD-TYPE	473	63	0.1 - 223.4 (24.5)

Figure S2. Get High-res Image Gene #51: 'PYCRL MUTATION STATUS' versus Clinical Feature #1: 'Time to Death'

Methods & Data

Input

Mutation data file = BRCA.mutsig.cluster.txt
Clinical data file = BRCA.clin.merged.picked.txt
Number of patients = 507
Number of significantly mutated genes = 100
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

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

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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)