Comparison of Germline versus Somatic BAP1 Mutations for Risk of Metastasis in Uveal Melanoma

Autor: Kathryn G. Ewens, Arupa Ganguly, Jennifer Richards-Yutz, Emilie Lalonde, Carol L. Shields
Rok vydání: 2018
Předmět:
Male
Uveal Neoplasms
Cancer Research
Somatic cell
Kaplan-Meier Estimate
Gene mutation
Germline
Metastasis
0302 clinical medicine
Medicine
Neoplasm Metastasis
Melanoma
Aged
80 and over
BAP1
Middle Aged
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
3. Good health
Oncology
030220 oncology & carcinogenesis
germline mutations
ocular/eye cancer
Female
Chromosomes
Human
Pair 3
uveal melanoma
Ubiquitin Thiolesterase
Research Article
Adult
Monosomy
Adolescent
DNA Copy Number Variations
lcsh:RC254-282
Young Adult
03 medical and health sciences
Germline mutation
Genetics
Humans
Genetic Predisposition to Disease
Germ-Line Mutation
Aged
Proportional Hazards Models
business.industry
Tumor Suppressor Proteins
medicine.disease
Mutation
030221 ophthalmology & optometry
Cancer research
somatic mutations
business
Zdroj: BMC Cancer
BMC Cancer, Vol 18, Iss 1, Pp 1-12 (2018)
ISSN: 1471-2407
DOI: 10.1186/s12885-018-5079-x
Popis: Background Germline mutations in BAP1 have been associated with BAP1-Tumor Predisposition Syndrome (BAP1-TPDS), a predisposition to multiple tumors within a family that includes uveal melanoma (UM), cutaneous melanoma, malignant mesothelioma and renal cell carcinoma. Alternatively, somatic mutations in BAP1 in UM have been associated with high risk for metastasis. In this study, we compare the risk of metastasis in UM that carry germline versus somatic BAP1 mutations and mutation-negative tumors. Methods DNA extracted from 142 UM and matched blood samples was sequenced using Sanger or next generation sequencing to identify BAP1 gene mutations. Results Eleven of 142 UM (8%) carried germline BAP1 mutations, 43 (30%) had somatic mutations, and 88 (62%) were mutation-negative. All BAP1 mutations identified in blood samples were also present in the matched UM. There were 52 unique mutations in 54 tumors. All were pathogenic or likely pathogenic. A comparison of tumors carrying somatic vs. germline mutations, or no mutations, showed a higher frequency of metastasis in tumors carrying somatic mutations: 74% vs. 36%, P=0.03 and 74% vs. 26% P
Databáze: OpenAIRE
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