Radiation Treatment Affects Chromosome Testing in Uveal Melanoma

Cancer Immunol Immunother

Essen

et al. 2017

Self Cite

Uveal melanoma (UM) is characterized by a number of genetic aberrations that follow a certain chronology and are tightly linked to tumor recurrence and survival. Loss of chromosome 3, bi-allelic loss of BAP1 expression, and gain in chromosome 8q have been associated with metastasis formation and death, while loss of chromosome 3 has been associated with the influx of macrophages and T cells. We used a set of genetically-classified UM to study immune infiltration in the context of their genetic evolution. We show in two independent cohorts that lack of BAP1 expression is associated with an increased density of CD3+ T cells and CD8+ T cells. The presence of extra copies of chromosome 8q in disomy 3 tumors with a normal BAP1 expression is associated with an increased influx of macrophages (but not T cells). Therefore, we propose that the genetic evolution of UM is associated with changes in the inflammatory phenotype. Early changes resulting in gain of chromosome 8q may activate macrophage infiltration, while sequential loss of BAP1 expression seems to drive T cell infiltration in UM.

Section: Discussionmentioning

confidence: 96%

Genetic evolution of uveal melanoma guides the development of an inflammatory microenvironment

Gezgin

Cancer Immunol Immunother

Essen

et al. 2017

Self Cite

“…; Dogrusöz et al. ). The advantage of karyotyping is that it provides information on all chromosomes in a single assay and allows the identification of structural and balanced chromosome abnormalities, in addition to numerical changes.…”

Section: Genetic Testsmentioning

confidence: 96%

“…Even in enucleated cases, larger tumour size was found to be correlated with a higher success rate of FISH in 213 primarily enucleated tumours (Dogrusöz et al. ). McCannel et al.…”

Section: Clinical Aspects Of Genetic Prognosticationmentioning

confidence: 99%

Genetic prognostication in uveal melanoma

Jager

2017

Acta Ophthalmologica

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Uveal melanoma (UM) is a rare tumour with a high propensity to metastasize. Although no effective treatment for metastases yet exists, prognostication in UM is relevant for patient counselling, planning of follow-up and stratification in clinical trials. Besides conventional clinicopathologic characteristics, genetic tumour features with prognostic significance have been identified. Non-random chromosome aberrations such as monosomy 3 and gain of chromosome 8q are strongly correlated with metastatic risk, while gain of chromosome 6p indicates a low risk. Recently, mutations in genes such as BAP1, SF3B1 and EIF1AX have been shown to be related to patient outcome. Genetics of UM is a rapidly advancing field, which not only contributes to the understanding of the pathogenesis of this cancer, but also results in further refinement of prognostication. Concomitantly, advances have been made in the use of genetic tests. New methods for genetic typing of UM have been developed. Despite the considerable progress made recently, many questions remain, such as those relating to the reliability of prognostic genetic tests, and the use of biopsied or previously irradiated tumour tissue for prognostication by genetic testing. In this article, we review genetic prognostic indicators in UM, also comparing available genetic tests, addressing the clinical application of genetic prognostication and discussing future perspectives for improving genetic prognostication in UM.

“…31 In 62 of these cases and four other tumors, single nucleotide polymorphism (SNP) array was performed as well.…”

Section: Cytogenetic Analysismentioning

confidence: 99%

The Prognostic Value of AJCC Staging in Uveal Melanoma Is Enhanced by Adding Chromosome 3 and 8q Status

Invest. Ophthalmol. Vis. Sci.

Bagger

Duinen

et al. 2017

Self Cite

Citation: Dogrusöz M, Bagger M, van Duinen SG, et al. The prognostic value of AJCC staging in uveal melanoma is enhanced by adding chromosome 3 and 8q status. Invest Ophthalmol Vis Sci. 2017;58:833-842. DOI:10.1167/ iovs.16-20212 PURPOSE. The American Joint Committee on Cancer (AJCC) staging system has been validated for use as a prognostic parameter in uveal melanoma (UM). We studied whether adding information regarding chromosome 3 and 8q status further enhances the prognostic value of this staging system. METHODS.We retrospectively studied a cohort of 522 patients who had been treated for UM in two different centers between 1999 and 2015. The mean follow-up time was 47.7 months. Cumulative incidence curves were generated and regression analyses were performed for different combinations of AJCC staging and chromosome status. Death due to UM metastases was the primary endpoint.RESULTS. In AJCC stage I cases, only patients with monosomy 3 as well as chromosome 8q gain died due to UM metastases (P < 0.001). Among patients with stage II and III tumors, those with monosomy 3 plus gain of chromosome 8q had the worst prognosis, whereas the clinical outcome of those with only one of these aberrations was intermediate (P < 0.001). Patients without monosomy 3 and 8q gain showed favorable prognosis, independent of their tumor's AJCC stage. In cases with monosomy 3, 8q gain, or both, adding AJCC stage improved the predictive value. Multivariable regression analyses demonstrated that AJCC staging and chromosome 3 and 8q status contain independent information about survival status.CONCLUSIONS. Combining information on AJCC staging and chromosome 3 and 8q status allows a more accurate prognostication in UM. We conclude that the prognostic value of the AJCC staging system can be improved by adding information regarding chromosome 3 and 8q status.