The Experts below are selected from a list of 3291 Experts worldwide ranked by ideXlab platform
Thomas Wiesner - One of the best experts on this subject based on the ideXlab platform.
-
multiple epithelioid spitz nevi or Tumors with loss of bap1 expression a clue to a Hereditary Tumor Syndrome
JAMA Dermatology, 2013Co-Authors: Klaus J Busam, Michelle Wanna, Thomas WiesnerAbstract:Importance Recently, a group of melanocytic Tumors with loss of BAP1 expression has been described. The lesions may occur sporadically or as part of a familial cancer Syndrome. They have distinct histopathologic features characterized by a nevuslike silhouette and cytologic composition of large epithelioid melanocytes with oval vesicular nuclei, distinct nucleoli, and abundant cytoplasm. The large melanocytes are immunohistochemically characterized by loss of nuclear labeling for BAP1. Observations We describe a 21-year-old patient with multiple combined melanocytic proliferations composed of both a nevus component with strong BAP1 expression and a large epithelioid melanocyte population with loss of BAP1 expression. The occurrence of multiple BAP1 loss melanocytic lesions raised concerns about a possible germline mutation. Sequence analysis of DNA from lesional and nonlesional skin confirmed a BAP1 germline mutation. Conclusions and Relevance The presence of multiple clinically banal–appearing melanocytic lesions with childhood onset suggests that the combined lesions with BAP1 loss large epithelioid melanocytes described herein are probably combined nevi. Our findings also illustrate how the detection of a histopathologically distinct melanocytic lesion, coupled with knowledge of its possible association with a Hereditary Tumor Syndrome, can lead to the suspicion and confirmation of a germline mutation.
Sebastian Walpole - One of the best experts on this subject based on the ideXlab platform.
-
comprehensive study of the clinical phenotype of germline bap1 variant carrying families worldwide
Journal of the National Cancer Institute, 2018Co-Authors: Sebastian Walpole, Robert Pilarski, Meredith Stautberg, Arnaud De La Fouchardiere, Colleen M Cebulla, Antonia L Pritchard, Frederick H Davidorf, Odile CabaretAbstract:Background: The BRCA1-associated protein-1 (BAP1) Tumor predisposition Syndrome (BAP1-TPDS) is a Hereditary Tumor Syndrome caused by germline pathogenic variants in BAP1 encoding a Tumor suppressor associated with uveal melanoma, mesothelioma, cutaneous melanoma, renal cell carcinoma, and cutaneous BAP1-inactivated melanocytic Tumors. However, the full spectrum of Tumors associated with the Syndrome is yet to be determined. Improved understanding of the BAP1-TPDS is crucial for appropriate clinical management of BAP1 germline variant carriers and their families, including genetic counseling and surveillance for new Tumors.Methods: We collated germline variant status, Tumor diagnoses, and information on BAP1 immunohistochemistry or loss of somatic heterozygosity on 106 published and 75 unpublished BAP1 germline variant-positive families worldwide to better characterize the genotypes and phenotypes associated with the BAP1-TPDS. Tumor spectrum and ages of onset were compared between missense and null variants. All statistical tests were two-sided.Results: The 181 families carried 140 unique BAP1 germline variants. The collated data confirmed the core Tumor spectrum associated with the BAP1-TPDS and showed that some families carrying missense variants can exhibit this phenotype. A variety of noncore BAP1-TPDS-associated Tumors were found in families of variant carriers. Median ages of onset of core Tumor types were lower in null than missense variant carriers for all Tumors combined (P<.001), mesothelioma (P<.001), cutaneous melanoma (P<.001), and nonmelanoma skin cancer (P<.001).Conclusions: This analysis substantially increases the number of pathogenic BAP1 germline variants and refines the phenotype. It highlights the need for a curated registry of germline variant carriers for proper assessment of the clinical phenotype of the BAP1-TPDS and pathogenicity of new variants, thus guiding management of patients and informing areas requiring further research.
Odile Cabaret - One of the best experts on this subject based on the ideXlab platform.
-
comprehensive study of the clinical phenotype of germline bap1 variant carrying families worldwide
Journal of the National Cancer Institute, 2018Co-Authors: Sebastian Walpole, Robert Pilarski, Meredith Stautberg, Arnaud De La Fouchardiere, Colleen M Cebulla, Antonia L Pritchard, Frederick H Davidorf, Odile CabaretAbstract:Background: The BRCA1-associated protein-1 (BAP1) Tumor predisposition Syndrome (BAP1-TPDS) is a Hereditary Tumor Syndrome caused by germline pathogenic variants in BAP1 encoding a Tumor suppressor associated with uveal melanoma, mesothelioma, cutaneous melanoma, renal cell carcinoma, and cutaneous BAP1-inactivated melanocytic Tumors. However, the full spectrum of Tumors associated with the Syndrome is yet to be determined. Improved understanding of the BAP1-TPDS is crucial for appropriate clinical management of BAP1 germline variant carriers and their families, including genetic counseling and surveillance for new Tumors.Methods: We collated germline variant status, Tumor diagnoses, and information on BAP1 immunohistochemistry or loss of somatic heterozygosity on 106 published and 75 unpublished BAP1 germline variant-positive families worldwide to better characterize the genotypes and phenotypes associated with the BAP1-TPDS. Tumor spectrum and ages of onset were compared between missense and null variants. All statistical tests were two-sided.Results: The 181 families carried 140 unique BAP1 germline variants. The collated data confirmed the core Tumor spectrum associated with the BAP1-TPDS and showed that some families carrying missense variants can exhibit this phenotype. A variety of noncore BAP1-TPDS-associated Tumors were found in families of variant carriers. Median ages of onset of core Tumor types were lower in null than missense variant carriers for all Tumors combined (P<.001), mesothelioma (P<.001), cutaneous melanoma (P<.001), and nonmelanoma skin cancer (P<.001).Conclusions: This analysis substantially increases the number of pathogenic BAP1 germline variants and refines the phenotype. It highlights the need for a curated registry of germline variant carriers for proper assessment of the clinical phenotype of the BAP1-TPDS and pathogenicity of new variants, thus guiding management of patients and informing areas requiring further research.
Klaus J Busam - One of the best experts on this subject based on the ideXlab platform.
-
multiple epithelioid spitz nevi or Tumors with loss of bap1 expression a clue to a Hereditary Tumor Syndrome
JAMA Dermatology, 2013Co-Authors: Klaus J Busam, Michelle Wanna, Thomas WiesnerAbstract:Importance Recently, a group of melanocytic Tumors with loss of BAP1 expression has been described. The lesions may occur sporadically or as part of a familial cancer Syndrome. They have distinct histopathologic features characterized by a nevuslike silhouette and cytologic composition of large epithelioid melanocytes with oval vesicular nuclei, distinct nucleoli, and abundant cytoplasm. The large melanocytes are immunohistochemically characterized by loss of nuclear labeling for BAP1. Observations We describe a 21-year-old patient with multiple combined melanocytic proliferations composed of both a nevus component with strong BAP1 expression and a large epithelioid melanocyte population with loss of BAP1 expression. The occurrence of multiple BAP1 loss melanocytic lesions raised concerns about a possible germline mutation. Sequence analysis of DNA from lesional and nonlesional skin confirmed a BAP1 germline mutation. Conclusions and Relevance The presence of multiple clinically banal–appearing melanocytic lesions with childhood onset suggests that the combined lesions with BAP1 loss large epithelioid melanocytes described herein are probably combined nevi. Our findings also illustrate how the detection of a histopathologically distinct melanocytic lesion, coupled with knowledge of its possible association with a Hereditary Tumor Syndrome, can lead to the suspicion and confirmation of a germline mutation.
Antonia L Pritchard - One of the best experts on this subject based on the ideXlab platform.
-
comprehensive study of the clinical phenotype of germline bap1 variant carrying families worldwide
Journal of the National Cancer Institute, 2018Co-Authors: Sebastian Walpole, Robert Pilarski, Meredith Stautberg, Arnaud De La Fouchardiere, Colleen M Cebulla, Antonia L Pritchard, Frederick H Davidorf, Odile CabaretAbstract:Background: The BRCA1-associated protein-1 (BAP1) Tumor predisposition Syndrome (BAP1-TPDS) is a Hereditary Tumor Syndrome caused by germline pathogenic variants in BAP1 encoding a Tumor suppressor associated with uveal melanoma, mesothelioma, cutaneous melanoma, renal cell carcinoma, and cutaneous BAP1-inactivated melanocytic Tumors. However, the full spectrum of Tumors associated with the Syndrome is yet to be determined. Improved understanding of the BAP1-TPDS is crucial for appropriate clinical management of BAP1 germline variant carriers and their families, including genetic counseling and surveillance for new Tumors.Methods: We collated germline variant status, Tumor diagnoses, and information on BAP1 immunohistochemistry or loss of somatic heterozygosity on 106 published and 75 unpublished BAP1 germline variant-positive families worldwide to better characterize the genotypes and phenotypes associated with the BAP1-TPDS. Tumor spectrum and ages of onset were compared between missense and null variants. All statistical tests were two-sided.Results: The 181 families carried 140 unique BAP1 germline variants. The collated data confirmed the core Tumor spectrum associated with the BAP1-TPDS and showed that some families carrying missense variants can exhibit this phenotype. A variety of noncore BAP1-TPDS-associated Tumors were found in families of variant carriers. Median ages of onset of core Tumor types were lower in null than missense variant carriers for all Tumors combined (P<.001), mesothelioma (P<.001), cutaneous melanoma (P<.001), and nonmelanoma skin cancer (P<.001).Conclusions: This analysis substantially increases the number of pathogenic BAP1 germline variants and refines the phenotype. It highlights the need for a curated registry of germline variant carriers for proper assessment of the clinical phenotype of the BAP1-TPDS and pathogenicity of new variants, thus guiding management of patients and informing areas requiring further research.