Effect of Heterogeneous Distribution of Monosomy 3 on Prognosis in Uveal Melanoma

Bronkhorst, Inge H. G.; Maat, Willem; Jordanova, Ekaterina S.; Kroes, Wilma G. M.; Schalij‐Delfos, Nicoline E.; Luyten, Gregorius P M; Jager, Martine J.

doi:10.5858/2010-0477-oar1

Cited by 35 publications

(30 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The authors report two patients with genetic imbalance in 20% of tumor cells who survived for over 100 months, but also hypothesized that these patients might develop metastases in the long run, and that minimal genetic imbalances (of 5%-10%) could lead to development of metastatic disease. Bronkhorst et al 19 also report that tumors with 5% of monosomy 3 correlate to a high risk of metastatic disease using a centromere probe. However, in their study, they state that a threshold of 30% for monosomy 3 predicts high risk of metastasis more accurately.…”

Section: Discussionmentioning

confidence: 98%

Higher Percentage of FISH-Determined Monosomy 3 and 8q Amplification in Uveal Melanoma Cells relate to Poor Patient Prognosis

Bosch

Beek²,

Vaarwater³

et al. 2012

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

PURPOSE. To investigate the relation between patient survival and incrementally increasing percentages of fluorescence in situ hybridization-determined complete loss of chromosome 3 (monosomy 3) and gain of chromosome 8q in primary uveal melanoma cells.METHODS. Clinicopathological factors were related to diseasefree survival. Fluorescence in situ hybridization was performed using probes on chromosomes 1, 3, 6, and 8. The percentages of UM cells with monosomy 3 or chromosome 8q gain were classified in groups with incrementally increasing percentages and related to disease-free survival. Correlations between clinical factors and cytogenetic aberrations were also analyzed.RESULTS. Two-hundred twenty choroidal and ciliary body melanomas were analyzed. The following proved to be significant predictors of survival in univariate analysis: older patient age (P ¼ 0.003); large tumor diameter (P < 0.001); mixed cell type (P ¼ 0.001); presence of closed microvascular loops (P < 0.001); loss of chromosome 1p (P ¼ 0.006); monosomy 3 (P < 0.001); gain of 6p (P < 0.001); and gain of chromosome 8q (P < 0.001). Multivariate Cox analysis displayed monosomy 3 (Hazard ratio [HR] 2.83, P ¼ 0.002) and gain of chromosome 8q (HR 3.13, P ¼ 0.002) as the most important independent prognostic factors of poor survival, followed by older patient age (HR 1.02, P ¼ 0.017). Increasing percentages of monosomy 3 and gain of chromosome 8q in tumor cells showed a correlation with worse prognosis (Logrank test 49.9 and 40.4, both P < 0.001) and increased number of additional copies of 8q correlated with shorter disease-free interval (Log-rank test 45.7, P < 0.001). CONCLUSIONS.A high percentage monosomy 3 and chromosome 8q gain in primary UM cells showed a strong relation with poor disease-free survival compared with low percentage aberrations. (Invest Ophthalmol Vis Sci.

show abstract

Section: Discussionmentioning

confidence: 98%

Higher Percentage of FISH-Determined Monosomy 3 and 8q Amplification in Uveal Melanoma Cells relate to Poor Patient Prognosis

Bosch

Beek²,

Vaarwater³

et al. 2012

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

show abstract

“…[82][83][84][85][86] Furthermore, it does not fit well with the concept of clonal evolution. 87,88 Recent evidence does indeed suggest that this model may be too simple, and that different clones of malignant melanocytes may evolve and co-exist within UM, with some having the potential to override or dominate others.…”

Section: The Hallmarks Of Cancermentioning

confidence: 99%

Molecular pathology of uveal melanoma

Coupland

Lake

Zeschnigk

et al. 2012

Eye

150

106

View full text Add to dashboard Cite

Like other cancers, uveal melanomas (UM) are characterised by an uncontrolled, clonal, cellular proliferation, occurring as a result of numerous genetic, and epigenetic aberrations. Signalling pathways known to be disrupted in UM include: (1) the retinoblastoma pathway, probably as a result of cyclin D1 overexpression; p53 signalling, possibly as a consequence of MDM2 overexpression; and the P13K/AKT and mitogen-activated protein kinase/extracellular signal-related kinase pathway pathways that are disturbed as a result of PTEN and GNAQ/11 mutations, respectively. Characteristic chromosomal abnormalities are common and include 6p gain, associated with a good prognosis, as well as 1p loss, 3 loss, and 8q gain, which correlate with high mortality. These are identified by techniques such as fluorescence in situ hybridisation, comparative genomic hybridisation, microsatellite analysis, multiplex ligationdependent probe amplification, and singlenucleotide polymorphisms. UM can also be categorised by their gene expression profiles as class 1 or class 2, the latter correlating with poor survival, as do BRCA1-associated protein-1 (BAP1) inactivating mutations. Genetic testing of UM has enhanced prognostication, especially when results are integrated with histological and clinical data. The identification of abnormal signalling pathways, genes and proteins in UM opens the way for target-based therapies, improving prospects for conserving vision and prolonging life.

show abstract

“…22 Monosomy 7 by FISH and chimerism by variable number of cytosine adenine (CA) repeat analysis were determined in expanded MSC before and after HSCT, respectively. 23,24 MSC gene expression and function was investigated using MSCs obtained at passage 2-3 and 3-5, respectively.…”

Section: Mesenchymal Stromal Cell Expansion and Characterizationmentioning

confidence: 99%

Gene-expression and in vitro function of mesenchymal stromal cells are affected in juvenile myelomonocytic leukemia

et al. 2015

View full text Add to dashboard Cite

An aberrant interaction between hematopoietic stem cells and mesenchymal stromal cells has been linked to disease and shown to contribute to the pathophysiology of hematologic malignancies in murine models. Juvenile myelomonocytic leukemia is an aggressive malignant disease affecting young infants. Here we investigated the impact of juvenile myelomonocytic leukemia on mesenchymal stromal cells. Mesenchymal stromal cells were expanded from bone marrow samples of patients at diagnosis (n=9) and after hematopoietic stem cell transplantation (n=7; from 5 patients) and from healthy children (n=10). Cells were characterized by phenotyping, differentiation, gene expression analysis (of controls and samples obtained at diagnosis) and in vitro functional studies assessing immunomodulation and hematopoietic support. Mesenchymal stromal cells from patients did not differ from controls in differentiation capacity nor did they differ in their capacity to support in vitro hematopoiesis. Deep-SAGE sequencing revealed differential mRNA expression in patient-derived samples, including genes encoding proteins involved in immunomodulation and cell-cell interaction. Selected gene expression normalized during remission after successful hematopoietic stem cell transplantation. Whereas natural killer cell activation and peripheral blood mononuclear cell proliferation were not differentially affected, the suppressive effect on monocyte to dendritic cell differentiation was increased by mesenchymal stromal cells obtained at diagnosis, but not at time of remission. This study shows that active juvenile myelomonocytic leukemia affects the immune responserelated gene expression and function of mesenchymal stromal cells. In contrast, the differential gene expression of hematopoiesis-related genes could not be supported by functional data. Decreased immune surveillance might contribute to the therapy resistance and progression in juvenile myelomonocytic leukemia.

show abstract

Effect of Heterogeneous Distribution of Monosomy 3 on Prognosis in Uveal Melanoma

Cited by 35 publications

References 29 publications

Higher Percentage of FISH-Determined Monosomy 3 and 8q Amplification in Uveal Melanoma Cells relate to Poor Patient Prognosis

Higher Percentage of FISH-Determined Monosomy 3 and 8q Amplification in Uveal Melanoma Cells relate to Poor Patient Prognosis

Molecular pathology of uveal melanoma

Gene-expression and in vitro function of mesenchymal stromal cells are affected in juvenile myelomonocytic leukemia

Contact Info

Product

Resources

About