A BAP1 Mutation in a Danish Family Predisposes to Uveal Melanoma and Other Cancers

Aoude, Lauren G.; Wadt, Karin; Bojesen, Anders; Crüger, Dorthe Gylling; Borg, Åke; Trent, Jeffrey M.; Brown, Kevin M.; Gerdes, Anne–Marie; Jönsson, Göran; Hayward, Nicholas K.

doi:10.1371/journal.pone.0072144

Cited by 50 publications

(52 citation statements)

References 17 publications

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“…However, further studies have implicated a range of other cancers as part of a possible BAP1 spectrum. In addition to RCC, possibly associated neoplasms include lung adenocarcinoma, meningioma, paraganglioma, breast cancer, neuroendocrine tumours, gastric cancer and basal cell carcinoma 22 24 25 27 28. These findings hint at the prospect of many other BAP1 associated cancers as more families are identified.…”

Section: Familial Melanoma Mutations and Risk Of Other Cancersmentioning

confidence: 97%

Melanoma genetics

2015

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Section: Familial Melanoma Mutations and Risk Of Other Cancersmentioning

confidence: 97%

Melanoma genetics

2015

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“…Notably, other cancers observed in this family include MM, CM, and meningioma. Since then, numerous reports have expanded on the discovery of germline mutations in families or individuals with these and other cancers [BAP1 tumor predisposition syndrome (TPDS)] (16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29). In the OMIM (Online Mendelian Inheritance in Man) database, the disorder is now referred to as TPDS #614327 (http://www.…”

Section: Somatic and Germline Mutations Of Bap1mentioning

confidence: 99%

BAP1, a tumor suppressor gene driving malignant mesothelioma

Cheung

Testa

2017

Transl. Lung Cancer Res.

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Like cancer generally, malignant mesothelioma (MM) is a genetic disease at the cellular level. DNA copy number analysis of mesothelioma specimens has revealed a number of recurrent sites of chromosomal loss, including 3p21.1, 9p21.3, and 22q12.2. The key inactivated driver genes located at 9p21.1 and 22q12.2 were discovered two decades ago as being the tumor suppressor loci CDKN2A and NF2, respectively. Only relatively recently was the BAP1 gene determined to be the driver gene at 3p21.1 that is somatically inactivated. In 2011, we reported germline mutations in BAP1 in two families with a high incidence of mesothelioma and other cancers such as uveal melanoma (UM). As a result of a flurry of research activity over the last 5-6 years, the BAP1 gene is now firmly linked causally to a novel tumor predisposition syndrome (TPDS) characterized by increased susceptibility to mesothelioma, UM, cutaneous melanoma (CM) and benign melanocytic tumors, as well as several other cancer types. Moreover, results from recent in vivo studies with genetically engineered Bap1-mutant mouse models and new functional studies have provided intriguing biological insights regarding BAP1's role in tumorigenesis. These and other recent findings offer new possibilities for novel preventative and therapeutic strategies for MM patients.

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“…After the reported filtering process [13] had been performed, 166 novel variants were identified for individual II.2 and 157 novel variants for individual II.3. Novel variants were defined as not seen in dbSNP (build 132) and not reported by the 1,000 Genomes Project (February 2012).…”

Section: Resultsmentioning

confidence: 99%

“…Whole-exome sequencing was carried out on blood samples from the two sisters, as previously described [13].…”

Section: Methodsmentioning

confidence: 99%

Germline RAD51B truncating mutation in a family with cutaneous melanoma

et al. 2015

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Known melanoma predisposition genes only account for around 40% of high-density melanoma families. Other rare mutations are likely to play a role in melanoma predisposition. RAD51B plays an important role in DNA repair through homologous recombination, and inactivation of RAD51B has been implicated in tumorigenesis. Thus RAD51B is a good candidate melanoma susceptibility gene, and previously, a germline splicing mutation in RAD51B has been identified in a family with early-onset breast cancer. In order to find genetic variants associated with melanoma predisposition, whole-exome sequencing was carried out on blood samples from a three-case cutaneous melanoma family. We identified a novel germline RAD51B nonsense mutation, and we demonstrate reduced expression of RAD51B in melanoma cells indicating inactivation of RAD51B. This is only the second report of a germline truncating RAD51B mutation. While this case report is consistent with melanoma being part of the RAD51B cancer spectrum further population-based screening of large case-control sample series will be needed to definitively establish if this is the case.

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A BAP1 Mutation in a Danish Family Predisposes to Uveal Melanoma and Other Cancers

Cited by 50 publications

References 17 publications

Melanoma genetics

Melanoma genetics

BAP1, a tumor suppressor gene driving malignant mesothelioma

Germline RAD51B truncating mutation in a family with cutaneous melanoma

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