Metastatic Disease in Polyploid Uveal Melanoma Patients Is Associated With<i>BAP1</i>Mutations

Yavuzyigitoglu, Serdar; Mensink, Hanneke W.; Smit, Kyra N.; Vaarwater, Jolanda; Verdijk, Robert M.; Beverloo, Berna; Brüggenwirth, Hennie T.; Marion, Ronald van; Dubbink, Hendrikus J.; Paridaens, Dion; Naus, Nicole; Klein, Annelies de; Kılıç, Emine

doi:10.1167/iovs.15-18608

Cited by 18 publications

(19 citation statements)

References 27 publications

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“…The Similar outcome presented by Ewens KG and his team in 2014 [21]. A deeper understanding of BAP1 mutation mentioned by Serdar Yavuzigitolu in 2016, Patients without BAP1 mutation would be diagnosed at the oldest age (mean, 66.9 years) [23] and BAP1 deficiency was still the most significant prognostic predictor of metastasis in patients with polyploidy UM karyotype [7].…”

Section: Um Patients' Prognosis With Genetic Aberrations Um Patients mentioning

confidence: 54%

“…Results showed there was in no difference prognosis with these main gene mutations between diploid and polyploidy UM patients. In addition, compared with diploid UM suggested BAP1 deficiency was still the most significant prognostic predictor of metastasis in patients with polyploidy UM karyotype (a 16-fold increased hazard ratio), polyploidy tumor had larger tumors (15.61 vs. 13.13 mm) and it was often associated with loss of chromosome 3 [7].…”

Section: Um Patients' Prognosis With Aberration Of Karyotypes Um Patimentioning

confidence: 97%

“…In the last century, researchers had already attempted to study the molecular genetic aberrations of UM metastases and correlated it with disease progression [7]. Prescher G and his team had studied 180 patients underwent primary enucleation for UM and 30 patients with monosmy 3 In 1996, based on univariate analysis they presented monosomy 3 was the most significant predictor of bad prognosis, followed by tumor diameter and location, suggested age and sex age had no additional predictive value [8].…”

Section: Aberration Of Karyotypes and Gene Mutations Were Confirmed Amentioning

confidence: 99%

“…Most of patients with uveal melanoma displayed the karyotypes were near-normal (diploid) with few nonrandom chromosomal changes like monosomy 3 and a gain of chromosome 8q [7], but some researches showed the karyotype would display polyploidy with a prevalence of 13% to 18% based on DNA content [11,12].…”

Section: Um Patients' Prognosis With Aberration Of Karyotypes Um Patimentioning

confidence: 99%

“…The karyotypes of UM patients were mainly displayed monosomy 3 and gain of chromosome 8q [7] which both showed bad prognosis [13][14][15][16][17][18][19]. Researchers had further investigated uveal melanomas prognostic situations with nonrandom alterations affecting chromosomes 1, 3, 6, and 8 and clinical features.…”

Section: Um Patients' Prognosis With Aberration Of Karyotypes Um Patimentioning

confidence: 99%

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Karyotype aberrations and gene mutations characteristics correlated it with UM prognosis

Mao¹,

Bin²

2017

New Front Ophthalmol

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Researchers tried to determined it whether the prognostic of the high incidence karyotype aberrations and gene mutations that had been displayed in uveal melanoma patients. Such as what the prognosis usually was about UM patients with loss of chromosome 3 (monosomy 3), polyploidy (>2N) or gain of chromosome 8q that were combined with/without the main gene mutations of BAP1 (BRCA-associated protein 1), EIF1AX (eukaryotic translation factor 1A), GNAQ (Guanine nucleotidebinding protein, q polypeptide), GNA11 (Guanine nucleotide-binding protein, subunit alpha-11) and SF3B1 (splicing factor 3 subunit B1). Through the literatures of recent years, researchers had suggested aberration of karyotypes and mutation of genes were both made in patients with different prognostic results than we had anticipated but allowed us to reassure patients with a good prognosis.

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Section: Um Patients' Prognosis With Genetic Aberrations Um Patients mentioning

confidence: 54%

Section: Um Patients' Prognosis With Aberration Of Karyotypes Um Patimentioning

confidence: 97%

Section: Aberration Of Karyotypes and Gene Mutations Were Confirmed Amentioning

confidence: 99%

Section: Um Patients' Prognosis With Aberration Of Karyotypes Um Patimentioning

confidence: 99%

Section: Um Patients' Prognosis With Aberration Of Karyotypes Um Patimentioning

confidence: 99%

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Karyotype aberrations and gene mutations characteristics correlated it with UM prognosis

Mao¹,

Bin²

2017

New Front Ophthalmol

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Chromosomal rearrangements in uveal melanoma: Chromothripsis

Poppelen

Yavuzyigitoglu

Smit

et al. 2018

Genes Chromosomes & Cancer

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Uveal melanoma (UM) is the most common primary intraocular malignancy in the Western world. Recurrent mutations in GNAQ, GNA11, CYSLTR2, PLCB4, BAP1, EIF1AX, and SF3B1 are described as well as non‐random chromosomal aberrations. Chromothripsis is a rare event in which chromosomes are shattered and rearranged and has been reported in a variety of cancers including UM. SNP arrays of 249 UM from patients who underwent enucleation, biopsy or endoresection were reviewed for the presence of chromothripsis. Chromothripsis was defined as ten or more breakpoints per chromosome involved. Genetic analysis of GNAQ, GNA11, BAP1, SF3B1, and EIF1AX was conducted using Sanger and next‐generation sequencing. In addition, immunohistochemistry for BAP1 was performed. Chromothripsis was detected in 7 out of 249 tumors and the affected chromosomes were chromosomes 3, 5, 6, 8, 12, and 13. The mean total of fragments per chromosome was 39.8 (range 12‐116). In 1 UM, chromothripsis was present in 2 different chromosomes. GNAQ, GNA11 or CYSLTR2 mutations were present in 6 of these tumors and 5 tumors harbored a BAP1 mutation and/or lacked BAP1 protein expression by immunohistochemistry. Four of these tumors metastasized and for the fifth only short follow‐up data are available. One of these metastatic tumors harbored an SF3B1 mutation. No EIF1AX mutations were detected in any of the tumors. To conclude, chromothripsis is a rare event in UM, occurring in 2.8% of samples and without significant association with mutations in any of the common UM driver genes.

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Genetics of Uveal Melanoma

et al. 2019

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Metastatic Disease in Polyploid Uveal Melanoma Patients Is Associated WithBAP1Mutations

Abstract: The prevalence of mutations in the UM related genes is not different in polyploid UM compared with diploid UM. Moreover, similar to patients with diploid UM, BAP1 mutation is the most significant prognostic predictor of metastasis in patients with polyploid UM.

Cited by 18 publications

References 27 publications

Karyotype aberrations and gene mutations characteristics correlated it with UM prognosis

Karyotype aberrations and gene mutations characteristics correlated it with UM prognosis

Chromosomal rearrangements in uveal melanoma: Chromothripsis

Genetics of Uveal Melanoma

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