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Anna-elina Lehesjoki - One of the best experts on this subject based on the ideXlab platform.
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Gynecological tumors in Mulibrey nanism and role for RING finger protein TRIM37 in the pathogenesis of ovarian fibrothecomas
Modern Pathology, 2009Co-Authors: Susann Karlberg, Jukka Kallijärvi, Anna-elina Lehesjoki, Marita Lipsanen-nyman, Heini Lassus, Ralf ButzowAbstract:Mulibrey nanism is an autosomal recessive Growth Disorder caused by mutations in the TRIM37 gene encoding a protein of unknown function. More than half of female patients with Mulibrey nanism develop benign mesenchymal tumors of ovarian sex cord–stromal origin. In this work, we characterize the gynecological tumors of female patients with Mulibrey nanism in detail. In addition to tumors of the fibrothecoma group, 18% (4/22) of the patients were observed with epithelial neoplasias, including 2 ovarian adenofibromas, 1 ovarian poorly differentiated adenocarcinoma and 1 endometrial adenocarcinoma. To investigate the possible involvement of TRIM37 alterations in the pathogenesis of sporadic fibrothecomas, we analyzed the TRIM37 cDNA for mutations and alternatively spliced transcripts and TRIM37 expression in fibrothecomas of women without Mulibrey nanism. No mutations in the open-reading frame of TRIM37 were detected. Two alternatively spliced variants were found, one lacking exon 23 and one exon 2. TRIM37 del2 was also found in normal ovary but in a proportion of sporadic fibrothecomas, the TRIM37 del2: TRIM37 ratio was increased. In normal ovary, TRIM37 was localized in the cytoplasm of stromal cells, especially theca cells surrounding developing follicles. TRIM37 transcript was found in all sporadic fibrothecomas examined, but 80% (20/25) of the tumors showed reduced or absent expression of TRIM37 protein. Allelic loss at the TRIM37 locus (17q22–23) was observed in 6% of sporadic fibrothecomas. Nearly half of the sporadic fibrothecomas showed evidence of CpG promoter methylation, suggesting promoter downregulation as one mechanism of reduced TRIM37 expression. In conclusion, inherited biallelic inactivation of TRIM37 (Mulibrey nanism) predisposes to both mesenchymal and epithelial ovarian tumors and dysregulation of TRIM37 may also be involved in the pathogenesis of sporadic fibrothecomas.
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the trim37 gene encodes a peroxisomal ring b box coiled coil protein classification of mulibrey nanism as a new peroxisomal Disorder
American Journal of Human Genetics, 2002Co-Authors: Jukka Kallijärvi, Kristiina Avela, Marita Lipsanennyman, Ismo Ulmanen, Anna-elina LehesjokiAbstract:Mulibrey nanism is a rare Growth Disorder of prenatal onset caused by mutations in the TRIM37 gene, which encodes a RING-B-box-coiled-coil protein. The pathogenetic mechanisms of mulibrey nanism are unknown. We have used transiently transfected cells and antibodies raised against the predicted TRIM37 protein to characterize the TRIM37 gene product and to determine its intracellular localization. We show that the human TRIM37 cDNA encodes a peroxisomal protein with an apparent molecular weight of 130 kD. Peroxisomal localization is compromised in mutant protein representing the major Finnish TRIM37 mutation but is retained in the protein representing the minor Finnish mutation. Colocalization of endogenous TRIM37 with peroxisomal markers was observed by double immunofluorescence staining in HepG2 and human intestinal smooth muscle cell lines. In human tissue sections, TRIM37 shows a granular cytoplasmic pattern. Endogenous TRIM37 is not imported into peroxisomes in peroxin 1 (PEX1−/−) and peroxin 5 (PEX5−/−) mutant fibroblasts but is imported normally in peroxin 7 (PEX7−/−) deficient fibroblasts, giving further evidence for a peroxisomal localization of TRIM37. Fibroblasts derived from patients with mulibrey nanism lack C-terminal TRIM37 immunoreactivity but stain normally for both peroxisomal matrix and membrane markers, suggesting apparently normal peroxisome biogenesis in patient fibroblasts. Taken together, this molecular evidence unequivocally indicates that TRIM37 is located in the peroxisomes, and Mulibrey nanism thus can be classified as a new peroxisomal Disorder.
Jukka Kallijärvi - One of the best experts on this subject based on the ideXlab platform.
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Gynecological tumors in Mulibrey nanism and role for RING finger protein TRIM37 in the pathogenesis of ovarian fibrothecomas
Modern Pathology, 2009Co-Authors: Susann Karlberg, Jukka Kallijärvi, Anna-elina Lehesjoki, Marita Lipsanen-nyman, Heini Lassus, Ralf ButzowAbstract:Mulibrey nanism is an autosomal recessive Growth Disorder caused by mutations in the TRIM37 gene encoding a protein of unknown function. More than half of female patients with Mulibrey nanism develop benign mesenchymal tumors of ovarian sex cord–stromal origin. In this work, we characterize the gynecological tumors of female patients with Mulibrey nanism in detail. In addition to tumors of the fibrothecoma group, 18% (4/22) of the patients were observed with epithelial neoplasias, including 2 ovarian adenofibromas, 1 ovarian poorly differentiated adenocarcinoma and 1 endometrial adenocarcinoma. To investigate the possible involvement of TRIM37 alterations in the pathogenesis of sporadic fibrothecomas, we analyzed the TRIM37 cDNA for mutations and alternatively spliced transcripts and TRIM37 expression in fibrothecomas of women without Mulibrey nanism. No mutations in the open-reading frame of TRIM37 were detected. Two alternatively spliced variants were found, one lacking exon 23 and one exon 2. TRIM37 del2 was also found in normal ovary but in a proportion of sporadic fibrothecomas, the TRIM37 del2: TRIM37 ratio was increased. In normal ovary, TRIM37 was localized in the cytoplasm of stromal cells, especially theca cells surrounding developing follicles. TRIM37 transcript was found in all sporadic fibrothecomas examined, but 80% (20/25) of the tumors showed reduced or absent expression of TRIM37 protein. Allelic loss at the TRIM37 locus (17q22–23) was observed in 6% of sporadic fibrothecomas. Nearly half of the sporadic fibrothecomas showed evidence of CpG promoter methylation, suggesting promoter downregulation as one mechanism of reduced TRIM37 expression. In conclusion, inherited biallelic inactivation of TRIM37 (Mulibrey nanism) predisposes to both mesenchymal and epithelial ovarian tumors and dysregulation of TRIM37 may also be involved in the pathogenesis of sporadic fibrothecomas.
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the trim37 gene encodes a peroxisomal ring b box coiled coil protein classification of mulibrey nanism as a new peroxisomal Disorder
American Journal of Human Genetics, 2002Co-Authors: Jukka Kallijärvi, Kristiina Avela, Marita Lipsanennyman, Ismo Ulmanen, Anna-elina LehesjokiAbstract:Mulibrey nanism is a rare Growth Disorder of prenatal onset caused by mutations in the TRIM37 gene, which encodes a RING-B-box-coiled-coil protein. The pathogenetic mechanisms of mulibrey nanism are unknown. We have used transiently transfected cells and antibodies raised against the predicted TRIM37 protein to characterize the TRIM37 gene product and to determine its intracellular localization. We show that the human TRIM37 cDNA encodes a peroxisomal protein with an apparent molecular weight of 130 kD. Peroxisomal localization is compromised in mutant protein representing the major Finnish TRIM37 mutation but is retained in the protein representing the minor Finnish mutation. Colocalization of endogenous TRIM37 with peroxisomal markers was observed by double immunofluorescence staining in HepG2 and human intestinal smooth muscle cell lines. In human tissue sections, TRIM37 shows a granular cytoplasmic pattern. Endogenous TRIM37 is not imported into peroxisomes in peroxin 1 (PEX1−/−) and peroxin 5 (PEX5−/−) mutant fibroblasts but is imported normally in peroxin 7 (PEX7−/−) deficient fibroblasts, giving further evidence for a peroxisomal localization of TRIM37. Fibroblasts derived from patients with mulibrey nanism lack C-terminal TRIM37 immunoreactivity but stain normally for both peroxisomal matrix and membrane markers, suggesting apparently normal peroxisome biogenesis in patient fibroblasts. Taken together, this molecular evidence unequivocally indicates that TRIM37 is located in the peroxisomes, and Mulibrey nanism thus can be classified as a new peroxisomal Disorder.
Ralf Butzow - One of the best experts on this subject based on the ideXlab platform.
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Gynecological tumors in Mulibrey nanism and role for RING finger protein TRIM37 in the pathogenesis of ovarian fibrothecomas
Modern Pathology, 2009Co-Authors: Susann Karlberg, Jukka Kallijärvi, Anna-elina Lehesjoki, Marita Lipsanen-nyman, Heini Lassus, Ralf ButzowAbstract:Mulibrey nanism is an autosomal recessive Growth Disorder caused by mutations in the TRIM37 gene encoding a protein of unknown function. More than half of female patients with Mulibrey nanism develop benign mesenchymal tumors of ovarian sex cord–stromal origin. In this work, we characterize the gynecological tumors of female patients with Mulibrey nanism in detail. In addition to tumors of the fibrothecoma group, 18% (4/22) of the patients were observed with epithelial neoplasias, including 2 ovarian adenofibromas, 1 ovarian poorly differentiated adenocarcinoma and 1 endometrial adenocarcinoma. To investigate the possible involvement of TRIM37 alterations in the pathogenesis of sporadic fibrothecomas, we analyzed the TRIM37 cDNA for mutations and alternatively spliced transcripts and TRIM37 expression in fibrothecomas of women without Mulibrey nanism. No mutations in the open-reading frame of TRIM37 were detected. Two alternatively spliced variants were found, one lacking exon 23 and one exon 2. TRIM37 del2 was also found in normal ovary but in a proportion of sporadic fibrothecomas, the TRIM37 del2: TRIM37 ratio was increased. In normal ovary, TRIM37 was localized in the cytoplasm of stromal cells, especially theca cells surrounding developing follicles. TRIM37 transcript was found in all sporadic fibrothecomas examined, but 80% (20/25) of the tumors showed reduced or absent expression of TRIM37 protein. Allelic loss at the TRIM37 locus (17q22–23) was observed in 6% of sporadic fibrothecomas. Nearly half of the sporadic fibrothecomas showed evidence of CpG promoter methylation, suggesting promoter downregulation as one mechanism of reduced TRIM37 expression. In conclusion, inherited biallelic inactivation of TRIM37 (Mulibrey nanism) predisposes to both mesenchymal and epithelial ovarian tumors and dysregulation of TRIM37 may also be involved in the pathogenesis of sporadic fibrothecomas.
Susann Karlberg - One of the best experts on this subject based on the ideXlab platform.
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Gynecological tumors in Mulibrey nanism and role for RING finger protein TRIM37 in the pathogenesis of ovarian fibrothecomas
Modern Pathology, 2009Co-Authors: Susann Karlberg, Jukka Kallijärvi, Anna-elina Lehesjoki, Marita Lipsanen-nyman, Heini Lassus, Ralf ButzowAbstract:Mulibrey nanism is an autosomal recessive Growth Disorder caused by mutations in the TRIM37 gene encoding a protein of unknown function. More than half of female patients with Mulibrey nanism develop benign mesenchymal tumors of ovarian sex cord–stromal origin. In this work, we characterize the gynecological tumors of female patients with Mulibrey nanism in detail. In addition to tumors of the fibrothecoma group, 18% (4/22) of the patients were observed with epithelial neoplasias, including 2 ovarian adenofibromas, 1 ovarian poorly differentiated adenocarcinoma and 1 endometrial adenocarcinoma. To investigate the possible involvement of TRIM37 alterations in the pathogenesis of sporadic fibrothecomas, we analyzed the TRIM37 cDNA for mutations and alternatively spliced transcripts and TRIM37 expression in fibrothecomas of women without Mulibrey nanism. No mutations in the open-reading frame of TRIM37 were detected. Two alternatively spliced variants were found, one lacking exon 23 and one exon 2. TRIM37 del2 was also found in normal ovary but in a proportion of sporadic fibrothecomas, the TRIM37 del2: TRIM37 ratio was increased. In normal ovary, TRIM37 was localized in the cytoplasm of stromal cells, especially theca cells surrounding developing follicles. TRIM37 transcript was found in all sporadic fibrothecomas examined, but 80% (20/25) of the tumors showed reduced or absent expression of TRIM37 protein. Allelic loss at the TRIM37 locus (17q22–23) was observed in 6% of sporadic fibrothecomas. Nearly half of the sporadic fibrothecomas showed evidence of CpG promoter methylation, suggesting promoter downregulation as one mechanism of reduced TRIM37 expression. In conclusion, inherited biallelic inactivation of TRIM37 (Mulibrey nanism) predisposes to both mesenchymal and epithelial ovarian tumors and dysregulation of TRIM37 may also be involved in the pathogenesis of sporadic fibrothecomas.
R L Field - One of the best experts on this subject based on the ideXlab platform.
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Growth Disorder and physical properties of znsnn2
Applied Physics Letters, 2013Co-Authors: Nathaniel Feldberg, James D Aldous, W M Linhart, Laurie J Phillips, K Durose, P A Stampe, R J Kennedy, David O Scanlon, Gulin Vardar, R L FieldAbstract:We examine ZnSnN2, a member of the class of materials contemporarily termed “earth-abundant element semiconductors,” with an emphasis on evaluating its suitability for photovoltaic applications. It is predicted to crystallize in an orthorhombic lattice with an energy gap of 2 eV. Instead, using molecular beam epitaxy to deposit high-purity, single crystal as well as highly textured polycrystalline thin films, only a monoclinic structure is observed experimentally. Far from being detrimental, we demonstrate that the cation sublattice Disorder which inhibits the orthorhombic lattice has a profound effect on the energy gap, obviating the need for alloying to match the solar spectrum.
