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Oncogenic GNAQ mutations are not correlated with disease-free survival in uveal melanoma.

Bauer J, Kilic E, Vaarwater J, Bastian BC, Garbe C, de Klein A - Br. J. Cancer (2009)

Bottom Line: Univariate and multivariate analysis showed that GNAQ mutation status was not significantly correlated with DFS.The GNAQ mutation status is not suitable to predict DFS.However, the high frequency of GNAQ mutations may render it a promising target for therapeutic intervention.

View Article: PubMed Central - PubMed

Affiliation: Department of Dermatology, University of Tübingen Medical Center, Liebermeisterstr. 25, Tübingen 72076, Germany. mail@j-bauer.de

ABSTRACT

Background: Recently, oncogenic G protein alpha subunit q (GNAQ) mutations have been described in about 50% of uveal melanomas and in the blue nevi of the skin.

Methods: GNAQ exon 5 was amplified from 75 ciliary body and choroidal melanoma DNAs and sequenced directly. GNAQ mutation status was correlated with disease-free survival (DFS), as well as other clinical and histopathological factors, and with chromosomal variations detected by FISH and CGH.

Results: Of the 75 tumour DNA samples analysed, 40 (53.3%) harboured oncogenic mutations in GNAQ codon 209. Univariate and multivariate analysis showed that GNAQ mutation status was not significantly correlated with DFS.

Conclusion: The GNAQ mutation status is not suitable to predict DFS. However, the high frequency of GNAQ mutations may render it a promising target for therapeutic intervention.

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Related in: MedlinePlus

Kaplan–Meier survival curve of GNAQ mutations vs wild type stratified for loss of chromosome 3. Black line represents mutated GNAQ, and the grey line represents wild type. The table shows the number of events and cases at risk over time at the respective time points.
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fig2: Kaplan–Meier survival curve of GNAQ mutations vs wild type stratified for loss of chromosome 3. Black line represents mutated GNAQ, and the grey line represents wild type. The table shows the number of events and cases at risk over time at the respective time points.

Mentions: Univariate analysis was performed for all parameters, showing a lower DFS for patients with loss of chromosome 3 and gain of chromosome 8q. Univariate analysis of GNAQ mutated cases compared with wild-type tumours did not show a significantly decreased DFS (P=0.273) (Figure 1). To examine the possibility that GNAQ mutations may affect the prognosis of patients with loss of one copy of chromosome 3, we calculated Kaplan–Meier survival curves of GNAQ status stratified for chromosome 3 status and performed log rank tests (P=0.559) (Figure 2). Disease-free survival was not modified by the presence of GNAQ mutations. In tumours with two copies of chromosome 3 the patients with a GNAQ mutation seemed to have a better prognosis, although it was not significant (P=0.097). Correlations between the clinical, chromosomal parameters and GNAQ mutation were calculated using Mann–Whitney and Fisher's exact tests (Table 1). We did not observe any significant correlations. When analysed in a multivariate model with GNAQ as a confounding variable, we obtained a hazard ratio of 1.07 with a P-value of 0.854 (data not shown).


Oncogenic GNAQ mutations are not correlated with disease-free survival in uveal melanoma.

Bauer J, Kilic E, Vaarwater J, Bastian BC, Garbe C, de Klein A - Br. J. Cancer (2009)

Kaplan–Meier survival curve of GNAQ mutations vs wild type stratified for loss of chromosome 3. Black line represents mutated GNAQ, and the grey line represents wild type. The table shows the number of events and cases at risk over time at the respective time points.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2736834&req=5

fig2: Kaplan–Meier survival curve of GNAQ mutations vs wild type stratified for loss of chromosome 3. Black line represents mutated GNAQ, and the grey line represents wild type. The table shows the number of events and cases at risk over time at the respective time points.
Mentions: Univariate analysis was performed for all parameters, showing a lower DFS for patients with loss of chromosome 3 and gain of chromosome 8q. Univariate analysis of GNAQ mutated cases compared with wild-type tumours did not show a significantly decreased DFS (P=0.273) (Figure 1). To examine the possibility that GNAQ mutations may affect the prognosis of patients with loss of one copy of chromosome 3, we calculated Kaplan–Meier survival curves of GNAQ status stratified for chromosome 3 status and performed log rank tests (P=0.559) (Figure 2). Disease-free survival was not modified by the presence of GNAQ mutations. In tumours with two copies of chromosome 3 the patients with a GNAQ mutation seemed to have a better prognosis, although it was not significant (P=0.097). Correlations between the clinical, chromosomal parameters and GNAQ mutation were calculated using Mann–Whitney and Fisher's exact tests (Table 1). We did not observe any significant correlations. When analysed in a multivariate model with GNAQ as a confounding variable, we obtained a hazard ratio of 1.07 with a P-value of 0.854 (data not shown).

Bottom Line: Univariate and multivariate analysis showed that GNAQ mutation status was not significantly correlated with DFS.The GNAQ mutation status is not suitable to predict DFS.However, the high frequency of GNAQ mutations may render it a promising target for therapeutic intervention.

View Article: PubMed Central - PubMed

Affiliation: Department of Dermatology, University of Tübingen Medical Center, Liebermeisterstr. 25, Tübingen 72076, Germany. mail@j-bauer.de

ABSTRACT

Background: Recently, oncogenic G protein alpha subunit q (GNAQ) mutations have been described in about 50% of uveal melanomas and in the blue nevi of the skin.

Methods: GNAQ exon 5 was amplified from 75 ciliary body and choroidal melanoma DNAs and sequenced directly. GNAQ mutation status was correlated with disease-free survival (DFS), as well as other clinical and histopathological factors, and with chromosomal variations detected by FISH and CGH.

Results: Of the 75 tumour DNA samples analysed, 40 (53.3%) harboured oncogenic mutations in GNAQ codon 209. Univariate and multivariate analysis showed that GNAQ mutation status was not significantly correlated with DFS.

Conclusion: The GNAQ mutation status is not suitable to predict DFS. However, the high frequency of GNAQ mutations may render it a promising target for therapeutic intervention.

Show MeSH
Related in: MedlinePlus