Frequent mutation of BAP1 in metastasizing uveal melanomas

J. William Harbour, Michael D. Onken, Elisha D O Roberson, Shenghui Duan, Li Cao, Lori A. Worley, M. Laurin Council, Katie A. Matatall, Cynthia Helms, Anne M. Bowcock

Research output: Contribution to journalArticle

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Abstract

Metastasis is a defining feature of malignant tumors and is the most common cause of cancer-related death, yet the genetics of metastasis are poorly understood. We used exome capture coupled with massively parallel sequencing to search for metastasis-related mutations in highly metastatic uveal melanomas of the eye. Inactivating somatic mutations were identified in the gene encoding BRCA1-associated protein 1 (BAP1) on chromosome 3p21.1 in 26 of 31 (84%) metastasizing tumors, including 15 mutations causing premature protein termination and 5 affecting its ubiquitin carboxyl terminal hydrolase domain. One tumor harbored a frameshift mutation that was germline in origin, thus representing a susceptibility allele. These findings implicate loss of BAP1 in uveal melanoma metastasis and suggest that the BAP1 pathway may be a valuable therapeutic target.

Original languageEnglish
Pages (from-to)1410-1413
Number of pages4
JournalScience
Volume330
Issue number6009
DOIs
StatePublished - Dec 3 2010
Externally publishedYes

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BRCA1 Protein
Neoplasm Metastasis
Mutation
Neoplasms
Exome
High-Throughput Nucleotide Sequencing
Frameshift Mutation
Chromosomes, Human, Pair 1
Hydrolases
Ubiquitin
Alleles
Uveal melanoma
Genes
Proteins

ASJC Scopus subject areas

  • General

Cite this

William Harbour, J., Onken, M. D., Roberson, E. D. O., Duan, S., Cao, L., Worley, L. A., ... Bowcock, A. M. (2010). Frequent mutation of BAP1 in metastasizing uveal melanomas. Science, 330(6009), 1410-1413. https://doi.org/10.1126/science.1194472

Frequent mutation of BAP1 in metastasizing uveal melanomas. / William Harbour, J.; Onken, Michael D.; Roberson, Elisha D O; Duan, Shenghui; Cao, Li; Worley, Lori A.; Council, M. Laurin; Matatall, Katie A.; Helms, Cynthia; Bowcock, Anne M.

In: Science, Vol. 330, No. 6009, 03.12.2010, p. 1410-1413.

Research output: Contribution to journalArticle

William Harbour, J, Onken, MD, Roberson, EDO, Duan, S, Cao, L, Worley, LA, Council, ML, Matatall, KA, Helms, C & Bowcock, AM 2010, 'Frequent mutation of BAP1 in metastasizing uveal melanomas', Science, vol. 330, no. 6009, pp. 1410-1413. https://doi.org/10.1126/science.1194472
William Harbour J, Onken MD, Roberson EDO, Duan S, Cao L, Worley LA et al. Frequent mutation of BAP1 in metastasizing uveal melanomas. Science. 2010 Dec 3;330(6009):1410-1413. https://doi.org/10.1126/science.1194472
William Harbour, J. ; Onken, Michael D. ; Roberson, Elisha D O ; Duan, Shenghui ; Cao, Li ; Worley, Lori A. ; Council, M. Laurin ; Matatall, Katie A. ; Helms, Cynthia ; Bowcock, Anne M. / Frequent mutation of BAP1 in metastasizing uveal melanomas. In: Science. 2010 ; Vol. 330, No. 6009. pp. 1410-1413.
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