Clinical Characteristics of Uveal Melanoma in Patients With Germline<i>BAP1</i>Mutations

Gupta, Mrinali P.; Lane, Anne Marie; DeAngelis, Margaret M.; Mayne, Katie; Crabtree, Margaux; Gragoudas, Evangelos S.; Kim, Ivana K.

doi:10.1001/jamaophthalmol.2015.1119

Cited by 106 publications

(94 citation statements)

References 35 publications

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“…Eighteen of 174 (10%) of the reported patients with germline BAP1 mutations had RCC with median age of diagnosis earlier than that seen in the general population (Table 1) (3, 5, 18, 25, 29, 37–40). Tumor tissue studies demonstrating LOH, somatic BAP1 mutations, and IHC staining all support an association between germline BAP1 mutation and RCC (Table 1) (39, 40, 44, 55–60).…”

Section: Resultsmentioning

confidence: 98%

Comprehensive review of BAP1 tumor predisposition syndrome with report of two new cases

et al. 2015

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The BRCA1-associated protein-1 (BAP1) tumor predisposition syndrome (BAP1-TPDS) is a recently identified hereditary cancer syndrome. Germline mutations in this tumor suppressor gene predispose families to the development of various malignancies. The molecular functions of the gene as well as the clinical phenotype of the syndrome are still being clarified. We sought to conduct a comprehensive review of published research into BAP1-TPDS to more thoroughly delineate the clinical implications of germline BAP1 mutations. We also report two additional families with germline BAP1 mutations. Current evidence demonstrates that germline BAP1 mutations predispose families to uveal melanoma, renal cell carcinoma, malignant mesothelioma, cutaneous melanoma, and possibly to a range of other cancers as well. Some of these cancers tend to be more aggressive, have a propensity to metastasize, and onset earlier in life in patients with BAP1 mutations as compared to non-predisposed patients with equivalent cancers. Although further research is necessary, this information can aid in the management, diagnosis, and therapy of these patients and their families, and highlights the importance of genetic counseling.

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Section: Resultsmentioning

confidence: 98%

Comprehensive review of BAP1 tumor predisposition syndrome with report of two new cases

et al. 2015

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“…Njauw et al have demonstrated that BAP1 mutations are more frequent among metastatic UM cases compared to non-metastatic UM controls (8% vs. 0%, p = 0.059), which has subsequently been confirmed in a separate cohort of 507 patients with OM. 5, 16 In addition, BAP1 mutations were more common in families with both CMM and UM compared to those with only CMM (29% vs. 0.52%; p= 0.003). 5 Gupta et al have recently reported that patients with UM, positive for germline BAP1 mutations, developed larger tumors (mean diameter, 15.9 vs 12.3 mm), exhibited higher rates of ciliary body involvement (75.0% vs 21.6%), had a higher metastatic potential (71.4% vs 18.0%) and had an increased frequency of family cancer history (especially for CM and OM) compared to controls.…”

Section: 2 Bap1 Tumor Syndromementioning

confidence: 97%

Hereditary melanoma: Update on syndromes and management

Soura

Eliades

Shannon

et al. 2016

Journal of the American Academy of Dermatology

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Recent advances in cancer genomics have enabled the discovery of many cancer predisposing genes that are being used to classify new familial melanoma/cancer syndromes. In addition to CDKN2A and CDK4, germline variants in TERT, MITF, and BAP1 have been added to the list of genes harboring melanoma-predisposing mutations. These newer entities may have escaped earlier description in part due to more advanced technologies and also in part due to their mixed cancer phenotype as opposed to a melanoma-focused syndrome. Dermatologists should be aware of, and able to recognize, the clinical signs exhibited by high-risk patients in different contexts. Personal and family history of cancer should always be sought in patients with multiple nevi, or positive history for melanoma, and should be updated yearly. Various features that are unique to specific disorders, such as the appearance of melanocytic BAP1-mutated atypical intradermal tumors (MBAITs) in cases of BAP1 melanoma syndrome, should also be recognized early. Such patients should be offered regular screenings with the use of dermoscopy and total body photography, as needed. More importantly, referral to other specialists may be needed if internal malignancy risk is suspected. It is important to have in mind that these patients tend to develop multiple melanomas, along with various internal organ malignancies, often at younger ages, therefore, a multidisciplinary approach to their cancer screening and treatment is ideal.

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“…Similar to Li-Fraumeni syndrome (33), there are a number of reported BAP1 mutation families where individuals are afflicted with more than one type of primary tumor (23,(42)(43)(44), strongly suggesting multiple tissue lineages being targeted by BAP1 deficiency. Cancer incidence data from published papers reporting germline BAP1 mutations indicated that the two most common primary tumors observed together are MM and UM (7 cases), melanocytic tumors and CM (7 patients), CM and basal cell carcinoma (7 patients), and MM and CM (6 cases) ( Table 1).…”

Section: Unique MM Clinical Characteristics Associated With Bap1 Mutamentioning

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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Clinical Characteristics of Uveal Melanoma in Patients With GermlineBAP1Mutations

Cited by 106 publications

References 35 publications

Comprehensive review of BAP1 tumor predisposition syndrome with report of two new cases

Comprehensive review of BAP1 tumor predisposition syndrome with report of two new cases

Hereditary melanoma: Update on syndromes and management

BAP1, a tumor suppressor gene driving malignant mesothelioma

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