Skin Cutaneous Melanoma: Correlation between copy number variations of arm-level result and selected clinical features<BR>(metastatic tumor cohort)

Skin Cutaneous Melanoma: Correlation between copy number variations of arm-level result and selected clinical features
(metastatic tumor cohort)

Maintained by TCGA GDAC Team (Broad Institute/MD Anderson Cancer Center/Harvard Medical School)

Overview

Introduction

This pipeline computes the correlation between significant arm-level copy number variations (cnvs) and selected clinical features.

Summary

Testing the association between copy number variation 73 arm-level results and 7 clinical features across 158 patients, 2 significant findings detected with Q value < 0.25.

18p gain cnv correlated to 'NEOPLASM.DISEASESTAGE'.
18q gain cnv correlated to 'NEOPLASM.DISEASESTAGE'.

Results

Overview of the results

Table 1. Get Full Table Overview of the association between significant copy number variation of 73 arm-level results and 7 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	DISTANT METASTASIS	LYMPH NODE METASTASIS	TUMOR STAGECODE	NEOPLASM DISEASESTAGE
	nCNV (%)	nWild-Type	logrank test	t-test	Fisher's exact test	Chi-square test	Chi-square test	t-test	Chi-square test
18p gain	19 (12%)	139	0.873 (1.00)	0.18 (1.00)	0.219 (1.00)	0.493 (1.00)	0.273 (1.00)		1.33e-05 (0.00577)
18q gain	11 (7%)	147	0.863 (1.00)	0.496 (1.00)	0.343 (1.00)	0.973 (1.00)	0.403 (1.00)		1.12e-06 (0.000489)
1p gain	22 (14%)	136	0.152 (1.00)	0.143 (1.00)	0.639 (1.00)	0.863 (1.00)	0.43 (1.00)		0.055 (1.00)
1q gain	54 (34%)	104	0.329 (1.00)	0.724 (1.00)	0.733 (1.00)	0.734 (1.00)	0.146 (1.00)		0.299 (1.00)
2p gain	13 (8%)	145	0.779 (1.00)	0.157 (1.00)	0.251 (1.00)	0.953 (1.00)	0.8 (1.00)		0.779 (1.00)
2q gain	11 (7%)	147	0.613 (1.00)	0.466 (1.00)	0.529 (1.00)	0.967 (1.00)	0.809 (1.00)		0.673 (1.00)
3p gain	16 (10%)	142	0.955 (1.00)	0.443 (1.00)	0.421 (1.00)	0.928 (1.00)	0.325 (1.00)		0.747 (1.00)
3q gain	21 (13%)	137	0.64 (1.00)	0.275 (1.00)	0.474 (1.00)	0.875 (1.00)	0.278 (1.00)		0.805 (1.00)
4p gain	16 (10%)	142	0.369 (1.00)	0.091 (1.00)	0.789 (1.00)	0.937 (1.00)	0.254 (1.00)		0.0565 (1.00)
4q gain	12 (8%)	146	0.389 (1.00)	0.0928 (1.00)	0.766 (1.00)	0.973 (1.00)	0.477 (1.00)		0.0471 (1.00)
5p gain	17 (11%)	141	0.0307 (1.00)	0.445 (1.00)	0.6 (1.00)	0.0224 (1.00)	0.656 (1.00)		0.659 (1.00)
5q gain	6 (4%)	152	0.354 (1.00)	0.227 (1.00)	1 (1.00)	0.992 (1.00)	0.347 (1.00)		0.53 (1.00)
6p gain	55 (35%)	103	0.648 (1.00)	0.513 (1.00)	0.171 (1.00)	0.735 (1.00)	0.416 (1.00)		0.43 (1.00)
6q gain	12 (8%)	146	0.716 (1.00)	0.8 (1.00)	0.541 (1.00)	0.249 (1.00)	0.922 (1.00)		0.44 (1.00)
7p gain	68 (43%)	90	0.558 (1.00)	0.843 (1.00)	0.414 (1.00)	0.0582 (1.00)	0.225 (1.00)		0.0522 (1.00)
7q gain	68 (43%)	90	0.913 (1.00)	0.285 (1.00)	0.87 (1.00)	0.0694 (1.00)	0.254 (1.00)		0.0138 (1.00)
8p gain	32 (20%)	126	0.71 (1.00)	0.404 (1.00)	0.32 (1.00)	0.0534 (1.00)	0.684 (1.00)		0.179 (1.00)
8q gain	48 (30%)	110	0.962 (1.00)	0.109 (1.00)	0.377 (1.00)	0.181 (1.00)	0.614 (1.00)		0.534 (1.00)
11p gain	9 (6%)	149	0.979 (1.00)	0.754 (1.00)	0.484 (1.00)	0.979 (1.00)	0.0485 (1.00)		0.695 (1.00)
11q gain	6 (4%)	152	0.253 (1.00)	0.878 (1.00)	0.405 (1.00)	0.992 (1.00)	0.833 (1.00)		0.533 (1.00)
12p gain	15 (9%)	143	0.647 (1.00)	0.098 (1.00)	0.407 (1.00)	0.105 (1.00)	0.606 (1.00)		0.239 (1.00)
12q gain	5 (3%)	153	0.957 (1.00)	0.557 (1.00)	0.649 (1.00)	0.995 (1.00)	0.0166 (1.00)		0.0181 (1.00)
13q gain	27 (17%)	131	0.35 (1.00)	0.373 (1.00)	0.525 (1.00)	0.605 (1.00)	0.102 (1.00)		0.084 (1.00)
14q gain	13 (8%)	145	0.725 (1.00)	0.983 (1.00)	0.57 (1.00)	0.96 (1.00)	0.819 (1.00)		0.885 (1.00)
15q gain	20 (13%)	138	0.778 (1.00)	0.788 (1.00)	1 (1.00)	0.898 (1.00)	0.811 (1.00)		0.805 (1.00)
16p gain	11 (7%)	147	0.995 (1.00)	0.665 (1.00)	1 (1.00)	0.96 (1.00)	0.899 (1.00)		0.558 (1.00)
16q gain	10 (6%)	148	0.819 (1.00)	0.993 (1.00)	0.741 (1.00)	0.967 (1.00)	0.857 (1.00)		0.84 (1.00)
17p gain	12 (8%)	146	0.362 (1.00)	0.584 (1.00)	1 (1.00)	0.199 (1.00)	0.788 (1.00)		0.0391 (1.00)
17q gain	20 (13%)	138	0.505 (1.00)	0.137 (1.00)	0.628 (1.00)	0.521 (1.00)	0.352 (1.00)		0.108 (1.00)
19p gain	10 (6%)	148	0.149 (1.00)	0.303 (1.00)	0.516 (1.00)	0.979 (1.00)	0.985 (1.00)		0.752 (1.00)
19q gain	12 (8%)	146	0.462 (1.00)	0.329 (1.00)	0.219 (1.00)	0.967 (1.00)	0.551 (1.00)		0.535 (1.00)
20p gain	48 (30%)	110	0.854 (1.00)	0.844 (1.00)	0.596 (1.00)	0.181 (1.00)	0.753 (1.00)		0.681 (1.00)
20q gain	59 (37%)	99	0.434 (1.00)	0.592 (1.00)	0.316 (1.00)	0.0419 (1.00)	0.948 (1.00)		0.639 (1.00)
21q gain	21 (13%)	137	0.548 (1.00)	0.932 (1.00)	0.474 (1.00)	0.276 (1.00)	0.236 (1.00)		0.0419 (1.00)
22q gain	43 (27%)	115	0.207 (1.00)	0.921 (1.00)	0.468 (1.00)	0.352 (1.00)	0.112 (1.00)		0.0413 (1.00)
Xq gain	3 (2%)	155	0.62 (1.00)	0.0699 (1.00)	0.28 (1.00)
1p loss	12 (8%)	146	0.107 (1.00)	0.919 (1.00)	1 (1.00)	0.973 (1.00)	0.237 (1.00)		0.23 (1.00)
1q loss	6 (4%)	152	0.961 (1.00)	0.464 (1.00)	0.68 (1.00)	0.988 (1.00)	0.511 (1.00)		0.84 (1.00)
2p loss	14 (9%)	144	0.0944 (1.00)	0.874 (1.00)	1 (1.00)	0.96 (1.00)	0.909 (1.00)		0.253 (1.00)
2q loss	13 (8%)	145	0.154 (1.00)	0.482 (1.00)	0.768 (1.00)	0.0149 (1.00)	0.923 (1.00)		0.132 (1.00)
3p loss	11 (7%)	147	0.446 (1.00)	0.412 (1.00)	0.753 (1.00)	0.979 (1.00)	0.0756 (1.00)		0.517 (1.00)
3q loss	11 (7%)	147	0.519 (1.00)	0.408 (1.00)	0.343 (1.00)	0.973 (1.00)	0.149 (1.00)		0.369 (1.00)
4p loss	16 (10%)	142	0.723 (1.00)	0.209 (1.00)	0.0588 (1.00)	0.0333 (1.00)	0.774 (1.00)		0.509 (1.00)
4q loss	16 (10%)	142	0.706 (1.00)	0.494 (1.00)	0.0588 (1.00)	0.0333 (1.00)	0.78 (1.00)		0.527 (1.00)
5p loss	22 (14%)	136	0.906 (1.00)	0.717 (1.00)	0.818 (1.00)	0.898 (1.00)	0.861 (1.00)		0.948 (1.00)
5q loss	33 (21%)	125	0.919 (1.00)	0.76 (1.00)	0.548 (1.00)	0.55 (1.00)	0.596 (1.00)		0.962 (1.00)
6p loss	14 (9%)	144	0.888 (1.00)	0.939 (1.00)	0.781 (1.00)	0.945 (1.00)	0.868 (1.00)		0.288 (1.00)
6q loss	64 (41%)	94	0.541 (1.00)	0.178 (1.00)	0.868 (1.00)	0.353 (1.00)	0.397 (1.00)		0.446 (1.00)
8p loss	21 (13%)	137	0.541 (1.00)	0.696 (1.00)	0.636 (1.00)	0.0873 (1.00)	0.499 (1.00)		0.298 (1.00)
8q loss	3 (2%)	155	0.263 (1.00)	0.63 (1.00)	0.0586 (1.00)	0.997 (1.00)	0.453 (1.00)		0.489 (1.00)
9p loss	91 (58%)	67	0.381 (1.00)	0.293 (1.00)	0.742 (1.00)	0.673 (1.00)	0.0234 (1.00)		0.0629 (1.00)
9q loss	72 (46%)	86	0.917 (1.00)	0.045 (1.00)	0.0337 (1.00)	0.424 (1.00)	0.466 (1.00)		0.0397 (1.00)
10p loss	69 (44%)	89	0.209 (1.00)	0.284 (1.00)	0.139 (1.00)	0.294 (1.00)	0.17 (1.00)		0.957 (1.00)
10q loss	76 (48%)	82	0.66 (1.00)	0.00546 (1.00)	0.194 (1.00)	0.268 (1.00)	0.239 (1.00)		0.928 (1.00)
11p loss	41 (26%)	117	0.0858 (1.00)	0.58 (1.00)	0.0938 (1.00)	0.0934 (1.00)	0.0935 (1.00)		0.0113 (1.00)
11q loss	44 (28%)	114	0.0345 (1.00)	0.636 (1.00)	0.103 (1.00)	0.134 (1.00)	0.089 (1.00)		0.00422 (1.00)
12p loss	9 (6%)	149	0.618 (1.00)	0.982 (1.00)	0.316 (1.00)	0.103 (1.00)	0.161 (1.00)		0.831 (1.00)
12q loss	17 (11%)	141	0.838 (1.00)	0.863 (1.00)	0.293 (1.00)	0.136 (1.00)	0.523 (1.00)		0.649 (1.00)
13q loss	25 (16%)	133	0.962 (1.00)	0.465 (1.00)	0.658 (1.00)	0.0919 (1.00)	0.125 (1.00)		0.617 (1.00)
14q loss	39 (25%)	119	0.58 (1.00)	0.32 (1.00)	0.452 (1.00)	0.11 (1.00)	0.465 (1.00)		0.259 (1.00)
15q loss	11 (7%)	147	0.795 (1.00)	0.287 (1.00)	0.753 (1.00)	0.00874 (1.00)	0.344 (1.00)		0.815 (1.00)
16p loss	12 (8%)	146	0.316 (1.00)	0.546 (1.00)	0.219 (1.00)	0.973 (1.00)	0.896 (1.00)		0.179 (1.00)
16q loss	28 (18%)	130	0.00482 (1.00)	0.854 (1.00)	0.402 (1.00)	0.122 (1.00)	0.683 (1.00)		0.173 (1.00)
17p loss	37 (23%)	121	0.277 (1.00)	0.421 (1.00)	0.701 (1.00)	0.276 (1.00)	0.708 (1.00)		0.62 (1.00)
17q loss	16 (10%)	142	0.094 (1.00)	0.983 (1.00)	1 (1.00)	0.105 (1.00)	0.145 (1.00)		0.409 (1.00)
18p loss	32 (20%)	126	0.465 (1.00)	0.489 (1.00)	0.843 (1.00)	0.768 (1.00)	0.0799 (1.00)		0.228 (1.00)
18q loss	28 (18%)	130	0.275 (1.00)	0.658 (1.00)	1 (1.00)	0.204 (1.00)	0.484 (1.00)		0.271 (1.00)
19p loss	13 (8%)	145	0.711 (1.00)	0.446 (1.00)	0.0346 (1.00)	0.0034 (1.00)	0.621 (1.00)		0.381 (1.00)
19q loss	15 (9%)	143	0.786 (1.00)	0.914 (1.00)	0.0997 (1.00)	0.0034 (1.00)	0.518 (1.00)		0.659 (1.00)
20p loss	6 (4%)	152	0.311 (1.00)	0.282 (1.00)	0.405 (1.00)	0.0316 (1.00)	0.974 (1.00)		0.573 (1.00)
21q loss	20 (13%)	138	0.786 (1.00)	0.94 (1.00)	0.628 (1.00)	0.887 (1.00)	0.846 (1.00)		0.133 (1.00)
22q loss	11 (7%)	147	0.88 (1.00)	0.692 (1.00)	0.343 (1.00)	0.96 (1.00)	0.97 (1.00)		0.37 (1.00)
Xq loss	6 (4%)	152	0.702 (1.00)	0.501 (1.00)	0.0348 (1.00)	0.995 (1.00)	0.975 (1.00)		0.846 (1.00)

'18p gain mutation analysis' versus 'NEOPLASM.DISEASESTAGE'

P value = 1.33e-05 (Chi-square test), Q value = 0.0058

Table S1. Gene #28: '18p gain mutation analysis' versus Clinical Feature #7: 'NEOPLASM.DISEASESTAGE'

nPatients	STAGE I	STAGE IA	STAGE IB	STAGE II	STAGE IIA	STAGE IIB	STAGE IIC	STAGE III	STAGE IIIA	STAGE IIIB	STAGE IIIC	STAGE IV
ALL	17	9	13	18	8	9	8	7	6	17	18	5
18P GAIN MUTATED	3	0	0	2	0	0	6	0	3	1	3	0
18P GAIN WILD-TYPE	14	9	13	16	8	9	2	7	3	16	15	5

Figure S1. Get High-res Image Gene #28: '18p gain mutation analysis' versus Clinical Feature #7: 'NEOPLASM.DISEASESTAGE'

'18q gain mutation analysis' versus 'NEOPLASM.DISEASESTAGE'

P value = 1.12e-06 (Chi-square test), Q value = 0.00049

Table S2. Gene #29: '18q gain mutation analysis' versus Clinical Feature #7: 'NEOPLASM.DISEASESTAGE'

nPatients	STAGE I	STAGE IA	STAGE IB	STAGE II	STAGE IIA	STAGE IIB	STAGE IIC	STAGE III	STAGE IIIA	STAGE IIIB	STAGE IIIC	STAGE IV
ALL	17	9	13	18	8	9	8	7	6	17	18	5
18Q GAIN MUTATED	1	0	0	0	0	0	5	0	2	0	2	0
18Q GAIN WILD-TYPE	16	9	13	18	8	9	3	7	4	17	16	5

Figure S2. Get High-res Image Gene #29: '18q gain mutation analysis' versus Clinical Feature #7: 'NEOPLASM.DISEASESTAGE'

Methods & Data

Input

Mutation data file = broad_values_by_arm.mutsig.cluster.txt
Clinical data file = SKCM-TM.clin.merged.picked.txt
Number of patients = 158
Number of significantly arm-level cnvs = 73
Number of selected clinical features = 7
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

Chi-square test

For multi-class clinical features (nominal or ordinal), Chi-square tests (Greenwood and Nikulin 1996) were used to estimate the P values using the 'chisq.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] Greenwood and Nikulin, A guide to chi-squared testing, Wiley, New York. ISBN 047155779X (1996)

[5] 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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