The DOI matches its Crossref record; 13 of the 13 references it cites were found in a registry or an index.
A Distinct Subset of Atypical Spitz Tumors is Characterized by BRAF Mutation and Loss of BAP1 Expression
Open accessAbstract
We recently reported that germline mutations in BAP1 cause a familial tumor syndrome characterized by high penetrance for melanocytic tumors with distinct clinical and histologic features. Melanocytic neoplasms in affected individuals harbored BRAF mutations, showed loss of BAP1 expression, and histologically resembled so-called "atypical Spitz tumors" (ASTs). ASTs are an ill-defined and probably heterogenous group of melanocytic tumors that display histologic features seen in both Spitz nevi and melanomas. Their biological behavior cannot be reliably predicted. In view of the histologic similarities of the familial tumors and ASTs, we hypothesized that a subset of ASTs might harbor genetic alterations seen in the familial tumors. To address this hypothesis, we analyzed 32 sporadic ASTs for BRAF mutations and for BAP1 expression. Nine (28%) sporadic ASTs showed loss of BAP1 expression, of which 8 (89%) had concomitant BRAF mutations. Only 1 of the BAP1-positive ASTs (4%) had a BRAF mutation (P<0.0001). BRAF-mutated, BAP1-negative tumors were primarily located in the dermis and were composed entirely or predominantly of epithelioid melanocytes with abundant amphophilic cytoplasm and well-defined cytoplasmic borders. Nuclei were commonly vesicular and exhibited substantial pleomorphism and conspicuous nucleoli. The combination of BRAF mutation and loss of nuclear BAP1 expression thus characterizes a subset of ASTs with distinct histologic features. The typical morphology of these tumors and BAP1 immunohistochemistry provide pathologic clues that will enable accurate identification of this subset. Future studies are necessary to determine whether this subset has a predictable clinical behavior.
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Cites
Distinct Sets of Genetic Alterations in Melanoma
Curtin, J. A., Fridlyand, J., Kageshita, T., Patel, H. N., Busam, K. J., Kutzner, H., Cho, K.-H., Aiba, S., Bröcker, E.-B., LeBoit, P. E., et al. (2005) · New England Journal of Medicine · doi:10.1056/nejmoa050092 · Cited by 2,747
Self-citationHigh frequency of BRAF mutations in nevi
Pollock, P. M., Harper, U. L., Hansen, K. S., Yudt, L. M., Stark, M., Robbins, C. M., Moses, T. Y., Hostetter, G., Wagner, U., Kakareka, J., et al. (2003) · Nature Genetics · doi:10.1038/ng1054 · Cited by 1,730
Frequent somatic mutations of GNAQ in uveal melanoma and blue naevi
Van Raamsdonk, C. D., Bezrookove, V., Green, G., Bauer, J., Gaugler, L., O’Brien, J. M., Simpson, E. M., Barsh, G. S., & Bastian, B. C. (2009) · Nature · doi:10.1038/nature07586 · Cited by 1,623
Self-citationSomatic Activation of KIT in Distinct Subtypes of Melanoma
Curtin, J. A., Busam, K., Pinkel, D., & Bastian, B. C. (2006) · Journal of Clinical Oncology · doi:10.1200/jco.2006.06.2984 · Cited by 1,616
Self-citationMutations in GNA11 in Uveal Melanoma
Van Raamsdonk, C. D., Griewank, K. G., Crosby, M. B., Garrido, M. C., Vemula, S., Wiesner, T., Obenauf, A. C., Wackernagel, W., Green, G., Bouvier, N., et al. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa1000584 · Cited by 1,476
Self-citationGermline mutations in BAP1 predispose to melanocytic tumors
Wiesner, T., Obenauf, A. C., Murali, R., Fried, I., Griewank, K. G., Ulz, P., Windpassinger, C., Wackernagel, W., Loy, S., Wolf, I., et al. (2011) · Nature Genetics · doi:10.1038/ng.910 · Cited by 725
Self-citationMutations and Copy Number Increase of HRAS in Spitz Nevi with Distinctive Histopathological Features
Bastian, B. C., LeBoit, P. E., & Pinkel, D. (2000) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)64609-3 · Cited by 455
Self-citationBarnhill, R. L., Argenyi, Z. B., From, L., Glass, L. F., Maize, J. C., Mihm, M. C., Rabkin, M. S., Ronan, S. G., White, W. L., & Piepkorn, M. (1999) · Human Pathology · doi:10.1016/s0046-8177(99)90193-4 · Cited by 426
Whiteman, D. C., Pavan, W. J., & Bastian, B. C. (2011) · Pigment Cell & Melanoma Research · doi:10.1111/j.1755-148x.2011.00880.x · Cited by 273
Self-citationBarnhill, R. L. (2006) · Modern Pathology · doi:10.1038/modpathol.3800519 · Cited by 235
Cited by
Kinase fusions are frequent in Spitz tumours and spitzoid melanomas
Wiesner, T., He, J., Yelensky, R., Esteve-Puig, R., Botton, T., Yeh, I., Lipson, D., Otto, G., Brennan, K., Murali, R., et al. (2014) · Nature Communications · doi:10.1038/ncomms4116 · Cited by 649
Self-citationCarbone, M., Yang, H., Pass, H. I., Krausz, T., Testa, J. R., & Gaudino, G. (2013) · Nature Reviews Cancer · doi:10.1038/nrc3459 · Cited by 590
Elder, D. E., Bastian, B. C., Cree, I. A., Massi, D., & Scolyer, R. A. (2020) · Archives of Pathology & Laboratory Medicine · doi:10.5858/arpa.2019-0561-ra · Cited by 502
Self-citationBAP1 cancer syndrome: malignant mesothelioma, uveal and cutaneous melanoma, and MBAITs
Carbone, M., Ferris, L. K., Baumann, F., Napolitano, A., Lum, C. A., Flores, E. G., Gaudino, G., Powers, A., Bryant-Greenwood, P., Krausz, T., et al. (2012) · Journal of Translational Medicine · doi:10.1186/1479-5876-10-179 · Cited by 323
Tumours associated with BAP1 mutations
Murali, R., Wiesner, T., & Scolyer, R. A. (2013) · Pathology · doi:10.1097/pat.0b013e32835d0efb · Cited by 270
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Metadata
- Authors
- Wiesner, T., Murali, R., Fried, I., Cerroni, L., Busam, K., Kutzner, H., & Bastian, B. C.
- Venue
- American Journal of Surgical Pathology
- Published
- 2012-06
- Volume
- 36
- Issue
- 6
- Pages
- 818-830
- ISSN
- 0147-5185 (ISSN-L)
- OpenAlex
- W2061694719
- Cited by
- 279
- References
- 13
- FWCI
- 11.36
- Type
- journal article
- Language
- en
- Open access
- green
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- Wiesner, T., Murali, R., Fried, I., Cerroni, L., Busam, K., Kutzner, H., & Bastian, B. C. (2012). A Distinct Subset of Atypical Spitz Tumors is Characterized by BRAF Mutation and Loss of BAP1 Expression. American Journal of Surgical Pathology. https://doi.org/10.1097/pas.0b013e3182498be5
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