Identification of Early-Onset Metastasis in SF3B1 Mutated Uveal Melanoma

Wojtek Drabarek; Job van Riet; Josephine Q N Nguyen; Kyra N Smit; Natasha M van Poppelen; Rick Jansen; Eva Medico-Salsench; Jolanda Vaarwater; Frank J Magielsen; Tom Brands; Bert Eussen; Thierry P P van den Bosch; Robert M Verdijk; Nicole C Naus; Dion Paridaens; Annelies de Klein; Erwin Brosens; Harmen J G van de Werken; Emine Kilic; Rotterdam Ocular Melanoma Study Group

doi:10.3390/cancers14030846

Identification of Early-Onset Metastasis in SF3B1 Mutated Uveal Melanoma

Wojtek Drabarek, Job van Riet, Josephine Q N Nguyen, Kyra N Smit, Natasha M van Poppelen, Rick Jansen, Eva Medico-Salsench, Jolanda Vaarwater, Frank J Magielsen, Tom Brands, Bert Eussen, Thierry P P van den Bosch, Robert M Verdijk, Nicole C Naus, Dion Paridaens, Annelies de Klein, Erwin Brosens, Harmen J G van de Werken, Emine Kilic, Rotterdam Ocular Melanoma Study Group

Orbita and oculoplastic surgery

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Approximately 25% of all uveal melanoma (UM) contain driver mutations in the gene encoding the spliceosome factor SF3B1, and whilst patients with such SF3B1 mutations generally have an intermediate risk on developing metastatic disease, a third of these patients develop early metastasis within 5 years after diagnosis. We therefore investigated whether clinical and/or genetic variables could be indicative of short progression-free survival (PFS < 60 months) or long PFS (PFS ≥ 60 months) for SF3B1-mutated (SF3B1mut) UM patients. We collected 146 SF3B1mut UM from our Rotterdam Ocular Melanoma Studygroup (ROMS) database and external published datasets. After stratification of all SF3B1mut UM using short PFS vs. long PFS, only largest tumor diameter (LTD) was significantly larger (mean: 17.7 mm (±2.8 SD) in the short PFS SF3B1mut group vs. the long PFS group (mean: 14.7 (±3.7 SD, p = 0.001). Combined ROMS and The Cancer Genome Atlas (TCGA) transcriptomic data were evaluated, and we identified SF3B1mut-specific canonical transcripts (e.g., a low expression of ABHD6 indicative for early-onset metastatic disease) or distinct expression of SF3B1mut UM aberrant transcripts, indicative of early- or late-onset or no metastatic SF3B1mut UM.

Originele taal-2	Engels
Pagina's (van-tot)	846
Tijdschrift	Cancers
Volume	14
Nummer van het tijdschrift	3
DOI's	https://doi.org/10.3390/cancers14030846
Status	Gepubliceerd - 8 feb. 2022

Trefwoorden

Aberrant splicing
Early metastasis
RNA-seq
SF3B1 mutation
Uveal melanoma

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10.3390/cancers14030846

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https://www.mendeley.com/catalogue/8fe0993a-e821-3fdf-b5d5-244c00882f79/

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Drabarek, W., van Riet, J., Nguyen, J. Q. N., Smit, K. N., van Poppelen, N. M., Jansen, R., Medico-Salsench, E., Vaarwater, J., Magielsen, F. J., Brands, T., Eussen, B., Bosch, T. P. P. V. D., Verdijk, R. M., Naus, N. C., Paridaens, D., de Klein, A., Brosens, E., van de Werken, H. J. G., Kilic, E., & Rotterdam Ocular Melanoma Study Group (2022). Identification of Early-Onset Metastasis in SF3B1 Mutated Uveal Melanoma. Cancers, 14(3), 846. https://doi.org/10.3390/cancers14030846

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title = "Identification of Early-Onset Metastasis in SF3B1 Mutated Uveal Melanoma",

abstract = "Approximately 25% of all uveal melanoma (UM) contain driver mutations in the gene encoding the spliceosome factor SF3B1, and whilst patients with such SF3B1 mutations generally have an intermediate risk on developing metastatic disease, a third of these patients develop early metastasis within 5 years after diagnosis. We therefore investigated whether clinical and/or genetic variables could be indicative of short progression-free survival (PFS < 60 months) or long PFS (PFS ≥ 60 months) for SF3B1-mutated (SF3B1mut) UM patients. We collected 146 SF3B1mut UM from our Rotterdam Ocular Melanoma Studygroup (ROMS) database and external published datasets. After stratification of all SF3B1mut UM using short PFS vs. long PFS, only largest tumor diameter (LTD) was significantly larger (mean: 17.7 mm (±2.8 SD) in the short PFS SF3B1mut group vs. the long PFS group (mean: 14.7 (±3.7 SD, p = 0.001). Combined ROMS and The Cancer Genome Atlas (TCGA) transcriptomic data were evaluated, and we identified SF3B1mut-specific canonical transcripts (e.g., a low expression of ABHD6 indicative for early-onset metastatic disease) or distinct expression of SF3B1mut UM aberrant transcripts, indicative of early- or late-onset or no metastatic SF3B1mut UM.",

keywords = "Aberrant splicing, Early metastasis, RNA-seq, SF3B1 mutation, Uveal melanoma",

author = "Wojtek Drabarek and {van Riet}, Job and Nguyen, {Josephine Q N} and Smit, {Kyra N} and {van Poppelen}, {Natasha M} and Rick Jansen and Eva Medico-Salsench and Jolanda Vaarwater and Magielsen, {Frank J} and Tom Brands and Bert Eussen and Bosch, {Thierry P P van den} and Verdijk, {Robert M} and Naus, {Nicole C} and Dion Paridaens and {de Klein}, Annelies and Erwin Brosens and {van de Werken}, {Harmen J G} and Emine Kilic and {Rotterdam Ocular Melanoma Study Group}",

year = "2022",

month = feb,

day = "8",

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language = "English",

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Drabarek, W, van Riet, J, Nguyen, JQN, Smit, KN, van Poppelen, NM, Jansen, R, Medico-Salsench, E, Vaarwater, J, Magielsen, FJ, Brands, T, Eussen, B, Bosch, TPPVD, Verdijk, RM, Naus, NC, Paridaens, D, de Klein, A, Brosens, E, van de Werken, HJG, Kilic, E & Rotterdam Ocular Melanoma Study Group 2022, 'Identification of Early-Onset Metastasis in SF3B1 Mutated Uveal Melanoma', Cancers, vol. 14, nr. 3, blz. 846. https://doi.org/10.3390/cancers14030846

TY - JOUR

T1 - Identification of Early-Onset Metastasis in SF3B1 Mutated Uveal Melanoma

AU - Drabarek, Wojtek

AU - van Riet, Job

AU - Nguyen, Josephine Q N

AU - Smit, Kyra N

AU - van Poppelen, Natasha M

AU - Jansen, Rick

AU - Medico-Salsench, Eva

AU - Vaarwater, Jolanda

AU - Magielsen, Frank J

AU - Brands, Tom

AU - Eussen, Bert

AU - Bosch, Thierry P P van den

AU - Verdijk, Robert M

AU - Naus, Nicole C

AU - Paridaens, Dion

AU - de Klein, Annelies

AU - Brosens, Erwin

AU - van de Werken, Harmen J G

AU - Kilic, Emine

AU - Rotterdam Ocular Melanoma Study Group

PY - 2022/2/8

Y1 - 2022/2/8

N2 - Approximately 25% of all uveal melanoma (UM) contain driver mutations in the gene encoding the spliceosome factor SF3B1, and whilst patients with such SF3B1 mutations generally have an intermediate risk on developing metastatic disease, a third of these patients develop early metastasis within 5 years after diagnosis. We therefore investigated whether clinical and/or genetic variables could be indicative of short progression-free survival (PFS < 60 months) or long PFS (PFS ≥ 60 months) for SF3B1-mutated (SF3B1mut) UM patients. We collected 146 SF3B1mut UM from our Rotterdam Ocular Melanoma Studygroup (ROMS) database and external published datasets. After stratification of all SF3B1mut UM using short PFS vs. long PFS, only largest tumor diameter (LTD) was significantly larger (mean: 17.7 mm (±2.8 SD) in the short PFS SF3B1mut group vs. the long PFS group (mean: 14.7 (±3.7 SD, p = 0.001). Combined ROMS and The Cancer Genome Atlas (TCGA) transcriptomic data were evaluated, and we identified SF3B1mut-specific canonical transcripts (e.g., a low expression of ABHD6 indicative for early-onset metastatic disease) or distinct expression of SF3B1mut UM aberrant transcripts, indicative of early- or late-onset or no metastatic SF3B1mut UM.

AB - Approximately 25% of all uveal melanoma (UM) contain driver mutations in the gene encoding the spliceosome factor SF3B1, and whilst patients with such SF3B1 mutations generally have an intermediate risk on developing metastatic disease, a third of these patients develop early metastasis within 5 years after diagnosis. We therefore investigated whether clinical and/or genetic variables could be indicative of short progression-free survival (PFS < 60 months) or long PFS (PFS ≥ 60 months) for SF3B1-mutated (SF3B1mut) UM patients. We collected 146 SF3B1mut UM from our Rotterdam Ocular Melanoma Studygroup (ROMS) database and external published datasets. After stratification of all SF3B1mut UM using short PFS vs. long PFS, only largest tumor diameter (LTD) was significantly larger (mean: 17.7 mm (±2.8 SD) in the short PFS SF3B1mut group vs. the long PFS group (mean: 14.7 (±3.7 SD, p = 0.001). Combined ROMS and The Cancer Genome Atlas (TCGA) transcriptomic data were evaluated, and we identified SF3B1mut-specific canonical transcripts (e.g., a low expression of ABHD6 indicative for early-onset metastatic disease) or distinct expression of SF3B1mut UM aberrant transcripts, indicative of early- or late-onset or no metastatic SF3B1mut UM.

KW - Aberrant splicing

KW - Early metastasis

KW - RNA-seq

KW - SF3B1 mutation

KW - Uveal melanoma

UR - https://www.mendeley.com/catalogue/8fe0993a-e821-3fdf-b5d5-244c00882f79/

U2 - 10.3390/cancers14030846

DO - 10.3390/cancers14030846

M3 - Article

C2 - 35159112

VL - 14

SP - 846

IS - 3

ER -

Identification of Early-Onset Metastasis in SF3B1 Mutated Uveal Melanoma

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