Frequency of germline mutations in cancer susceptibility genes in malignant mesothelioma

Vasiliki Panou, Meghana Gadiraju, Arthur Wolin, Caroline M Weipert, Emily Skarda, Aliya N Husain, Jyoti D Patel, Buerkley Rose, Viswateja Nelakuditi, Amy Knight Johnson, Maria Helgeson, David Fischer, Nanna Sulai, Kiran K Turaga, Dezheng Huo, Jeremy Segal, Sabah Kadri, Zejuan Li, Hedy L Kindler, Jane E Churpek

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Abstrakt

Purpose The aim of the current study was to determine the prevalence and clinical predictors of germline cancer susceptibility mutations in patients with malignant mesothelioma (MM). Methods We performed targeted capture and next-generation sequencing of 85 cancer susceptibility genes on germline DNA from 198 patients with pleural, peritoneal, and tunica vaginalis MM. Results Twenty-four germline mutations were identified in 13 genes in 23 (12%) of 198 patients. BAP1 mutations were the most common (n = 6; 25%). The remaining were in genes involved in DNA damage sensing and repair (n = 14), oxygen sensing (n = 2), endosome trafficking (n = 1), and cell growth (n = 1). Pleural site (odds ratio [OR], 0.23; 95% CI, 0.10 to 0.58; P < .01), asbestos exposure (OR, 0.28; 95% CI, 0.11 to 0.72; P < .01), and older age (OR, 0.95; 95% CI, 0.92 to 0.99; P = .01) were associated with decreased odds of carrying a germline mutation, whereas having a second cancer diagnosis (OR, 3.33; 95% CI, 1.22 to 9.07; P = .02) significantly increased the odds. The odds of carrying a mutation in BAP1 (OR, 1,658; 95% CI, 199 to 76,224; P < .001), BRCA2 (OR, 5; 95% CI, 1.0 to 14.7; P = .03), CDKN2A (OR, 53; 95% CI, 6 to 249; P < .001), TMEM127 (OR, 88; 95% CI, 1.7 to 1,105; P = .01), VHL (OR, 51; 95% CI, 1.1 to 453; P = .02), and WT1 (OR, 20; 95% CI, 0.5 to 135; P = .049) were significantly higher in MM cases than in a noncancer control population. Tumor sequencing identified mutations in a homologous recombination pathway gene in 52% (n = 29 of 54). Conclusion A significant proportion of patients with MM carry germline mutations in cancer susceptibility genes, especially those with peritoneal MM, minimal asbestos exposure, young age, and a second cancer diagnosis. These data support clinical germline genetic testing for patients with MM and provide a rationale for additional investigation of the homologous recombination pathway in MM.

OriginalsprogEngelsk
TidsskriftJournal of clinical oncology : official journal of the American Society of Clinical Oncology
Vol/bind36
Udgave nummerSuppl. 15
Sider (fra-til)8564-8564
Antal sider1
ISSN0732-183X
DOI
StatusUdgivet - 2018
BegivenhedASCO Annual Meeting 2018 - McCormick Place, Chicago, USA
Varighed: 1 jun. 20185 jun. 2018
http://www.asco.org

Konference

KonferenceASCO Annual Meeting 2018
LokationMcCormick Place
Land/OmrådeUSA
ByChicago
Periode01/06/201805/06/2018
Internetadresse

Bibliografisk note

Abstract no. 8564

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