Prevalence and Preliminary Validation of Screening Criteria to Identify Carriers of Germline BAP1 Mutations.
Adult
Aged
Aged, 80 and over
Female
Genetic Carrier Screening
/ methods
Genetic Predisposition to Disease
Germ-Line Mutation
Humans
Lung Neoplasms
/ diagnosis
Male
Melanoma
/ diagnosis
Mesothelioma
/ diagnosis
Mesothelioma, Malignant
Middle Aged
Prevalence
Prognosis
Skin Neoplasms
/ diagnosis
Tumor Suppressor Proteins
/ genetics
Ubiquitin Thiolesterase
/ genetics
Uveal Neoplasms
/ diagnosis
Young Adult
BRCA associated protein-1 (BAP1)
Genetic testing
Mesothelioma
Screening criteria
Journal
Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer
ISSN: 1556-1380
Titre abrégé: J Thorac Oncol
Pays: United States
ID NLM: 101274235
Informations de publication
Date de publication:
11 2019
11 2019
Historique:
received:
11
04
2019
revised:
27
06
2019
accepted:
08
07
2019
pubmed:
20
7
2019
medline:
26
8
2020
entrez:
20
7
2019
Statut:
ppublish
Résumé
Inherited mutations are easily detected factors that influence the disease courses and optimal treatment strategies of some cancers. Germline mutations in BRCA1 associated protein 1 (BAP1) are associated with unique disease profiles in mesothelioma, atypical spitz nevi, and uveal melanoma, but the patient characteristics of an unselected population of BAP1 carriers identified by an ascertainment prevalence study are unknown. We collected blood samples, cancer histories, and occupational exposures from 183 unselected patients with BAP1-related diseases. Clinical information for each patient was obtained from medical records. Germline DNA was extracted from blood samples and sequenced using a next-generation sequencing assay. We tested screening criteria developed to identify patients with a possible germline BAP1 mutation. Pathogenic or likely pathogenic germline BAP1 mutations were observed in 5 of 180 sequenced specimens and were exclusively found in patients identified by our screening criteria. Several patients with characteristics suspicious for a heritable deleterious mutation did not have a germline BAP1 mutation. The prevalence of pathogenic germline BAP1 mutations in patients with mesothelioma was 4.4% (95% confidence interval 1.1-11.1). Results from the first unselected prevalence ascertainment study of germline BAP1 alterations suggest that the frequency of this mutation is low among patients with mesothelioma. The proposed screening criteria successfully identified all patients with germline BAP1-mutant mesothelioma. These screening guidelines may assist physicians in selecting patients who would benefit from genetic testing. Future efforts should validate and refine these criteria and search for other germline mutations associated with mesothelioma and related diseases.
Identifiants
pubmed: 31323388
pii: S1556-0864(19)30559-3
doi: 10.1016/j.jtho.2019.07.002
pmc: PMC6823112
mid: NIHMS1051714
pii:
doi:
Substances chimiques
BAP1 protein, human
0
Tumor Suppressor Proteins
0
Ubiquitin Thiolesterase
EC 3.4.19.12
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Validation Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
1989-1994Subventions
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Informations de copyright
Copyright © 2019 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.
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