Abstract We describe an autosomal-dominant syndrome characterized by multiple non-pigmented, exophytic melanocytic nevi and an increased susceptibility for melanoma, caused by germline mutations in the histone deubiquitinase BAP1. To identify the causative alterations, we performed comprehensive genomic analyses in two unrelated families with numerous dermal nevi composed largely of large, epithelioid melanocytes with abundant amphophilic cytoplasm and large, pleomorphic, vesicular nuclei with prominent nucleoli. Both families each had one proband with uveal melanoma, and three probands in one family had cutaneous melanoma. Array-based comparative genomic hybridization (aCGH) revealed losses of parts of or the entire chromosome 3 in 11 of 22 neoplasms studied. Genotypic analyses revealed that the deletions invariably affected the chromosome from the unaffected parent. Genome partitioning of the minimally deleted region on chromosome 3p21 followed by massively parallel sequencing revealed two different inactivating germline mutations of the BAP1 tumor suppressor gene that in both families segregated with the phenotype. In almost all tumors the remaining wild type BAP1 allele was eliminated by deletion, separate inactivating mutations, or loss of heterozygosity. 35 of 40 nevi (88%) showed mutations in BRAF, while the uveal melanomas had mutations in GNAQ. Our data identify BAP1 as a highly penetrant susceptibility gene for melanocytic neoplasia. Somatic BAP1 mutations have recently been reported in uveal melanoma and linked to the metastatic phenotype. Our observation of frequent bi-allelic inactivation of BAP1 in nevi indicates that the role of BAP1 in melanocytic neoplasia is more complex, and may differ depending on other factors such as the type of melanocyte (uveal or cutaneous) and the co-existing oncogenic mutation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-125. doi:10.1158/1538-7445.AM2011-LB-125

Common acquired melanocytic nevi are benign neoplasms that are composed of small, uniform melanocytes and are typically present as flat or slightly elevated pigmented lesions on the skin. We describe two families with a new autosomal dominant syndrome characterized by multiple, skin-colored, elevated melanocytic tumors. In contrast to common acquired nevi, the melanocytic neoplasms in affected family members ranged histopathologically from epithelioid nevi to atypical melanocytic proliferations that showed overlapping features with melanoma. Some affected individuals developed uveal or cutaneous melanomas. Segregating with this phenotype, we found inactivating germline mutations of BAP1, which encodes a ubiquitin carboxy-terminal hydrolase. The majority of melanocytic neoplasms lost the remaining wild-type allele of BAP1 by various somatic alterations. In addition, we found BAP1 mutations in a subset of sporadic melanocytic neoplasms showing histological similarities to the familial tumors. These findings suggest that loss of BAP1 is associated with a clinically and morphologically distinct type of melanocytic neoplasm.

APMISVolume 117, Issue 2 p. 148-150 Syringocystadenocarcinoma papilliferum in situ originating from the perianal skin CORD LANGNER, CORD LANGNER Institute of Pathology, Medical University, Graz, AustriaSearch for more papers by this authorARTHUR OTT, ARTHUR OTT Institute of Pathology, Medical University, Graz, AustriaSearch for more papers by this author CORD LANGNER, CORD LANGNER Institute of Pathology, Medical University, Graz, AustriaSearch for more papers by this authorARTHUR OTT, ARTHUR OTT Institute of Pathology, Medical University, Graz, AustriaSearch for more papers by this author First published: 12 February 2009 https://doi.org/10.1111/j.1600-0463.2008.00027.xCitations: 19Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Citing Literature Volume117, Issue2February 2009Pages 148-150 RelatedInformation

Background:Melanoma incidence rates vary within Europe. The highest incidences are reported in Scandinavia, the lowest in the southern parts, but incidences themselves also vary within the different countries. Objective:We investigated the incidence of invasive cutaneous melanoma in Styria, a province of Austria, in the years 2001–2003. Methods:Data from 1,082 patients, 511 males and 571 females (mean age 58.2 years) with primary melanoma were collected. For each patient, information regarding residence was available, and therefore the geographic distribution of melanoma on district level was investigated with particular reference to the mean number of sun hours, mean altitude, number of companies with more than 200 employees and median income. Results:The mean annual incidence (age-standardized rate) was 24.5 per 100,000 (95% CI: 22.4–26.6), lifetime risk 1 in 52. Districts with a higher number of sun hours and higher altitude showed lower melanoma incidences. Higher median income was associated with higher melanoma incidence (p < 0.001). Conclusion:The high incidence of invasive melanoma in Styria is unclear and a causal relationship between higher income and melanoma incidence remains speculative. Further investigations, especially concerning lifestyle and environmental factors, may unravel additional causative factors.

Summary Background: Rising melanoma incidences have created the need of assessment of epidemiological and clinical data. Patients and methods: We investigated the natural history of invasive cutaneous melanoma in Styria, a province of Austria, in the years 2001–2003. 1082 patients, 511 men and 571 women, mean age 58.2 ± 16.7 years, were collected. Besides basic melanoma data, special histologic features such as regression structures, ulceration, microsatellites and vascular invasion were investigated. Furthermore, lymph node pathology in case of sentinel node biopsy and/or lymph node dissection was recorded. Results: Mean annual incidence (crude rate) was 28.6 per 100,000 inhabitants, age standardized rate 24.5 per 100,000 (95 % CI 22.4–26.6). Cumulative risk (0– 74 years) was 1.92, lifetime risk 1 in 52. Superficial spreading melanoma was the most common type in both sexes, men on the trunk and women on the extremities. Only 11 % of all melanomas were in easily visible areas. Median tumor thickness was 0.75 mm, ranging between 0.2 and 50.0 mm. Sentinel node biopsy was performed in 158 melanomas (14.6 %),and was positive in 22 %.Primary therapeutic lymph node dissection was performed in 19 patients, showing metastases in 18 patients. Conclusions: The investigation revealed an unclear high melanoma incidence for invasive melanomas in our province, requiring further investigation.

JDDG: Journal der Deutschen Dermatologischen GesellschaftVolume 5, Issue 4 Klinisch-epidemiologische Daten des invasiven kutanen Melanoms in der Steiermark, Österreich 2001–2003 Erika Richtig, Erika Richtig Univ.-Klinik für Dermatologie, Medizinische Universität Graz, ÖsterreichSearch for more papers by this authorArmin Gerger, Armin Gerger Medizinische Universitätsklinik, Abteilung für Onkologie, Medizinische Universität Graz, ÖsterreichSearch for more papers by this authorAndrea Berghold, Andrea Berghold Institut für medizinische Informatik, Statistik und Dokumentation, Medizinische Universität Graz, ÖsterreichSearch for more papers by this authorGerold Schwantzer, Gerold Schwantzer Institut für medizinische Informatik, Statistik und Dokumentation, Medizinische Universität Graz, ÖsterreichSearch for more papers by this authorArthur Ott, Arthur Ott Institut für Pathologie, Medizinische Universität Graz, ÖsterreichSearch for more papers by this authorHelmut Kerl, Helmut Kerl Univ.-Klinik für Dermatologie, Medizinische Universität Graz, ÖsterreichSearch for more papers by this authorJosef Smolle, Josef Smolle Institut für medizinische Informatik, Statistik und Dokumentation, Medizinische Universität Graz, ÖsterreichSearch for more papers by this author Erika Richtig, Erika Richtig Univ.-Klinik für Dermatologie, Medizinische Universität Graz, ÖsterreichSearch for more papers by this authorArmin Gerger, Armin Gerger Medizinische Universitätsklinik, Abteilung für Onkologie, Medizinische Universität Graz, ÖsterreichSearch for more papers by this authorAndrea Berghold, Andrea Berghold Institut für medizinische Informatik, Statistik und Dokumentation, Medizinische Universität Graz, ÖsterreichSearch for more papers by this authorGerold Schwantzer, Gerold Schwantzer Institut für medizinische Informatik, Statistik und Dokumentation, Medizinische Universität Graz, ÖsterreichSearch for more papers by this authorArthur Ott, Arthur Ott Institut für Pathologie, Medizinische Universität Graz, ÖsterreichSearch for more papers by this authorHelmut Kerl, Helmut Kerl Univ.-Klinik für Dermatologie, Medizinische Universität Graz, ÖsterreichSearch for more papers by this authorJosef Smolle, Josef Smolle Institut für medizinische Informatik, Statistik und Dokumentation, Medizinische Universität Graz, ÖsterreichSearch for more papers by this author First published: 19 March 2007 https://doi.org/10.1111/j.1610-0387.2007.06246_supp.xAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Volume5, Issue4April 2007 RelatedInformation