Prevalence of BRCA-1 associated protein 1 germline mutation in sporadic malignant pleural mesothelioma cases

Rusch, Andreas; Ziltener, Gabriela; Nackaerts, Kristiaan; Weder, Walter; Stahel, Rolf A.; Felley‐Bosco, Emanuela

doi:10.1016/j.lungcan.2014.10.017

Cited by 35 publications

(26 citation statements)

References 23 publications

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“…Variation in the sample population was consistent with the expected rate for an outbred population. These data provide support for two recent studies showing no known functionally significant BAP1 germline mutations in 78 MM patients (Rusch et al, 2015) and 103 MM cases (Betti et al, 2015).…”

Section: Resultssupporting

confidence: 88%

“…All detected SNPs were in Hardy-Weinberg equilibrium. Assuming a prevalence of germline BAP1 mutations of 7.7% in MM patients as previously described (Testa et al, 2011), the Poisson distribution probability that there were no mutations in the 115 cases was p = 0.0001, or p = 10 − 10 if all three studies on sporadic MM were combined (Testa et al, 2011;Betti et al, 2015;Rusch et al, 2015). Conversely, the upper 95% confidence limit for zero mutations out of 115 cases was 2.6% or 1.0% with all 3 studies combined.…”

Section: Resultsmentioning

confidence: 95%

“…Of note these two cases were reported to have no known asbestos exposure. However, subsequent studies of nearly 200 sporadic European MM cases have not identified any relevant germline BAP1 mutations (Betti et al, 2015;Rusch et al, 2015). The identification of genetic susceptibility markers for MM, that are independent of asbestos exposure, could impact on the screening of asbestos-exposed individuals and has the potential to affect the medico-legal responsibilities of governments and the asbestos manufacturing/production industry.…”

Section: Introductionmentioning

confidence: 99%

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Absence of germline mutations in BAP1 in sporadic cases of malignant mesothelioma

Sneddon

Leon

Dick

et al. 2015

Gene

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Malignant mesothelioma (MM) is a uniformly fatal tumour caused predominantly by exposure to asbestos. It is not known why some exposed individuals get mesothelioma and others do not. There is some epidemiological evidence of host susceptibility. BAP1 gene somatic mutations and allelic loss are common in mesothelioma and recently a BAP1 cancer syndrome was described in which affected individuals and families had an increased risk of cancer of multiple types, including MM. To determine if BAP1 mutations could underlie any of the sporadic mesothelioma cases in our cohort of patients, we performed targeted deep sequencing of the BAP1 exome on the IonTorrent Proton sequencer in 115 unrelated MM cases. No exonic germline BAP1 mutations of known functional significance were observed, further supporting the notion that sporadic germline BAP1 mutations are not relevant to the genetic susceptibility of MM.

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Section: Resultssupporting

confidence: 88%

Section: Resultsmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

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Absence of germline mutations in BAP1 in sporadic cases of malignant mesothelioma

Sneddon

Leon

Dick

et al. 2015

Gene

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“…b Leukemia, prostate, lung, thyroid, breast, larynx, colon, stomach, pancreas (BAP1 unmutated families); Breast, salivary gland, stomach, throat (BAP1 mutated families). Some authors report breast cancer as potential BAP1 syndrome-related cancer [22] …”

Section: Case D-ii-3) Somatic Mutations In Exonmentioning

confidence: 99%

“…Germline BAP1 alterations are a rare event in sporadic MM [10,18,[21][22][23]. The majority are benign polymorphisms (SNPs) or variants of unknown significance (VUS) [4,5,23].…”

Section: Introductionmentioning

confidence: 99%

Mesothelioma families without inheritance of a BAP1 predisposing mutation

et al. 2016

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This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. (n=1), and unknown (n=1). These family units without inheritance of a BAP1 predisposing mutation expand the number of unmutated germline BAP1 families with multiple mesothelioma cases. This suggests that besides the exposure to asbestos other currently unknown genetic or epigenetic factors may be responsible for the high incidence of mesothelioma in BAP1-unmutated families.

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Sensitivity to asbestos is increased in patients with mesothelioma and pathogenic germline variants in BAP1 or other DNA repair genes

Betti

Aspesi

Ferrante

et al. 2018

Genes Chromosomes & Cancer

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Pathogenic germline variants in the BAP1 tumor suppressor gene can cause a cancer syndrome called BAP1 tumor predisposition syndrome (BAP1‐TPDS), which is characterized by predisposition to mesothelioma, melanoma, renal cell carcinoma, basal cell carcinoma, and other tumors. Other genes that may predispose to mesothelioma are CDKN2A and DNA repair genes. Asbestos exposure has often been reported in patients with malignant pleural mesothelioma (MPM) and germline variants in BAP1, but this exposure has never been quantified. We aimed to search for germline variants in BAP1 among 25 new Italian probands with suspected BAP1‐TPDS, summarize the prevalence of these variants in 39 Italian patients with familial MPM and other tumors recruited over a 5‐year period, and compare cumulative asbestos exposure in 14 patients with MPM and pathogenic germline variants in BAP1, CDKN2A, or DNA repair genes with that of 67 patients without germline variants in 94 cancer‐predisposing genes. We report here a new pathogenic germline variant in BAP1: c.783 + 2 T > C. The prevalence of pathogenic germline variants in BAP1 was 7.7% among patients with familial MPM (3/39). Patients with pathogenic germline variants in BAP1, CDKN2A, or DNA repair genes showed lower cumulative asbestos exposure than patients without germline variants in 94 cancer‐predisposing genes (P = .00002). This suggests an interaction between genetic risk factors and asbestos in the development of mesothelioma.

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Prevalence of BRCA-1 associated protein 1 germline mutation in sporadic malignant pleural mesothelioma cases

Abstract: Taking into account previous similar screenings, the prevalence of germline BAP1 mutations in sporadic MPM patients can be estimated around 1-2%, suggesting a minor role of germline BAP1 mutation in the pathogenesis of sporadic MPM.

Cited by 35 publications

References 23 publications

Absence of germline mutations in BAP1 in sporadic cases of malignant mesothelioma

Absence of germline mutations in BAP1 in sporadic cases of malignant mesothelioma

Mesothelioma families without inheritance of a BAP1 predisposing mutation

Sensitivity to asbestos is increased in patients with mesothelioma and pathogenic germline variants in BAP1 or other DNA repair genes

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