Identification of Early-Onset Metastasis in SF3B1 Mutated Uveal Melanoma

Wojtek Drabarek; Job van Riet; on behalf of the Rotterdam Ocular Melanoma Study Group; 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

doi:10.3390/cancers14030846

Identification of Early-Onset Metastasis in SF3B1 Mutated Uveal Melanoma

Wojtek Drabarek, Job van Riet, on behalf of the Rotterdam Ocular Melanoma Study Group, 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

^*Corresponding author for this work

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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 (SF3B1^mut) UM patients. We collected 146 SF3B1^mut UM from our Rotterdam Ocular Melanoma Studygroup (ROMS) database and external published datasets. After stratification of all SF3B1^mut 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 SF3B1^mut 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 SF3B1^mut-specific canonical transcripts (e.g., a low expression of ABHD6 indicative for early-onset metastatic disease) or distinct expression of SF3B1^mut UM aberrant transcripts, indicative of early-or late-onset or no metastatic SF3B1^mut UM.

Original language	English
Article number	846
Journal	Cancers
Volume	14
Issue number	3
DOIs	https://doi.org/10.3390/cancers14030846
Publication status	Published - 8 Feb 2022

Bibliographical note

Funding Information:
Funding: This research was funded by the Henkes Foundation [SF3B1-2018], Collaborative Ophthalmic Research Rotterdam [5.2.0 and 5.2.1], Landelijke Stichting voor Blinden en Slechtzienden [2018-4] and Stichting Beheer Het Schild [2018-4].

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© 2022 by the authors. Licensee MDPI, Basel, Switzerland.

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Drabarek, W., van Riet, J., on behalf of the Rotterdam Ocular Melanoma Study Group, 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., van den Bosch, T. P. P., Verdijk, R. M., Naus, N. C., Paridaens, D., de Klein, A., Brosens, E., van de Werken, H. J. G., & Kilic, E. (2022). Identification of Early-Onset Metastasis in SF3B1 Mutated Uveal Melanoma. Cancers, 14(3), [846]. https://doi.org/10.3390/cancers14030846

@article{32baeb0c795249848c5ec7b6ad6817c3,

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.",

author = "Wojtek Drabarek and {van Riet}, Job and {on behalf of the Rotterdam Ocular Melanoma Study Group} 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 {van den Bosch}, {Thierry P.P.} 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",

note = "Funding Information: Funding: This research was funded by the Henkes Foundation [SF3B1-2018], Collaborative Ophthalmic Research Rotterdam [5.2.0 and 5.2.1], Landelijke Stichting voor Blinden en Slechtzienden [2018-4] and Stichting Beheer Het Schild [2018-4]. Publisher Copyright: {\textcopyright} 2022 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2022",

month = feb,

day = "8",

doi = "10.3390/cancers14030846",

language = "English",

volume = "14",

journal = "Cancers",

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Drabarek, W, van Riet, J, on behalf of the Rotterdam Ocular Melanoma Study Group, Nguyen, JQN, Smit, KN, van Poppelen, NM, Jansen, R, Medico-Salsench, E , Vaarwater, J, Magielsen, FJ, Brands, T, Eussen, B, van den Bosch, TPP , Verdijk, RM , Naus, NC , Paridaens, D , de Klein, A , Brosens, E , van de Werken, HJG & Kilic, E 2022, 'Identification of Early-Onset Metastasis in SF3B1 Mutated Uveal Melanoma', Cancers, vol. 14, no. 3, 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 - on behalf of the Rotterdam Ocular Melanoma Study Group

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 - van den Bosch, Thierry P.P.

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

N1 - Funding Information: Funding: This research was funded by the Henkes Foundation [SF3B1-2018], Collaborative Ophthalmic Research Rotterdam [5.2.0 and 5.2.1], Landelijke Stichting voor Blinden en Slechtzienden [2018-4] and Stichting Beheer Het Schild [2018-4]. Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

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.

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U2 - 10.3390/cancers14030846

DO - 10.3390/cancers14030846

M3 - Article

AN - SCOPUS:85124090774

VL - 14

JO - Cancers

JF - Cancers

SN - 2072-6694

IS - 3

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ER -

Identification of Early-Onset Metastasis in SF3B1 Mutated Uveal Melanoma

Abstract

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