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Twinkal C Pansuriya - One of the best experts on this subject based on the ideXlab platform.
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somatic mosaic idh1 and idh2 mutations are associated with enchondroma and spindle cell hemangioma in ollier disease and Maffucci Syndrome
Nature Genetics, 2011Co-Authors: Twinkal C Pansuriya, Jan Oosting, Ronald Van Eijk, Pio Dadamo, Maayke A J H Van Ruler, Marieke L Kuijjer, Annemarie Cletonjansen, Jolieke G Van Oosterwijk, Sofie L J Verbeke, Danielle MeijerAbstract:Ollier disease and Maffucci Syndrome are non-hereditary skeletal disorders characterized by multiple enchondromas (Ollier disease) combined with spindle cell hemangiomas (Maffucci Syndrome). We report somatic heterozygous mutations in IDH1 (c.394C>T encoding an R132C substitution and c.395G>A encoding an R132H substitution) or IDH2 (c.516G>C encoding R172S) in 87% of enchondromas (benign cartilage tumors) and in 70% of spindle cell hemangiomas (benign vascular lesions). In total, 35 of 43 (81%) subjects with Ollier disease and 10 of 13 (77%) with Maffucci Syndrome carried IDH1 (98%) or IDH2 (2%) mutations in their tumors. Fourteen of 16 subjects had identical mutations in separate lesions. Immunohistochemistry to detect mutant IDH1 R132H protein suggested intraneoplastic and somatic mosaicism. IDH1 mutations in cartilage tumors were associated with hypermethylation and downregulated expression of several genes. Mutations were also found in 40% of solitary central cartilaginous tumors and in four chondrosarcoma cell lines, which will enable functional studies to assess the role of IDH1 and IDH2 mutations in tumor formation.
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incidence predictive factors and prognosis of chondrosarcoma in patients with ollier disease and Maffucci Syndrome an international multicenter study of 161 patients
Oncologist, 2011Co-Authors: Suzan Hm Verdegaal, Twinkal C Pansuriya, Robert J Grimer, Paul C Jutte, David Biau, I C M Van Der Geest, Harzem Ozger, Mikel San Julian, Andreas LeithnerAbstract:Background. Enchondromatosis is characterized by the presence of multiple benign cartilage lesions in bone. While Ollier disease is typified by multiple enchondromas, in Maffucci Syndrome these are associated with hemangiomas. Studies evaluating the predictive value of clinical symptoms for development of secondary chondrosarcoma and prognosis are lacking. This multi-institute study evaluates the clinical characteristics of patients, to get better insight on behavior and prognosis of these diseases. Method.Aretrospectivestudywasconductedusingclinical dataof144Ollierand17Maffuccipatientsfrom13European centers and one national databank supplied by members of the European Musculoskeletal Oncology Society. Results. Patients had multiple enchondromas in the hands and feet only (group I, 18%), in long bones including scapula and pelvis only (group II, 39%), and in both small and long/flat bones (group III, 43%), respectively. The overall incidence of chondrosarcoma thus far is 40%. In group I, only 4 patients (15%) developed chondrosarcoma, in contrast to 27 patients (43%) in group II and 26 patients (46%) in group III, respectively. The risk of developing chondrosarcoma is increased when enchondromas are located in the pelvis (odds ratio, 3.8; p 0.00l). Conclusions. Overall incidence of development of chondrosarcoma is 40%, but may, due to age-dependency, increase when considered as a lifelong risk. Patients with
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Maffucci Syndrome a genome wide analysis using high resolution single nucleotide polymorphism and expression arrays on four cases
Genes Chromosomes and Cancer, 2011Co-Authors: Twinkal C Pansuriya, Jan Oosting, Suzan Hm Verdegaal, Pancras Cw Hogendoorn, Raf Sciot, Adrienne M Flanagan, Larsgunnar Kindblom, Karoly Szuhai, Judith V.m.g. BovéeAbstract:Ollier disease and Maffucci Syndrome are rare, nonhereditary skeletal disorders characterized by the presence of multiple enchondromas with (Maffucci) or without (Ollier) co-existing multiple hemangiomas of soft tissue. Enchondromas can progress toward central chondrosarcomas. PTH1R mutations are found in a small subset of Ollier patients. The genetic deficit in Maffucci Syndrome is unknown. Here, we report the first genome-wide analysis using Affymetrix SNP 6.0 array on Maffucci enchondromas (n = 4) and chondrosarcomas (n = 2) from four cases. Results were compared to a previously studied cohort of Ollier patients (n = 37). We found no loss of heterozygosity (LOH) or common copy number alterations shared by all enchondromas, with the exception of some copy number variations. As expected, chondrosarcomas were found to have multiple genomic imbalances. This is similar to conventional solitary and Ollier-related enchondromas and chondrosarcomas and supports the multistep genetic progression model. Expression profiling using Illumina BeadArray-v3 chip revealed that cartilaginous tumors in Maffucci patients are more similar to such tumors in Ollier patients than to sporadic cartilage tumors. Point mutations in a single gene or other copy number neutral genomic changes might play a role in enchondromagenesis.
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Loss-of-function mutations in PTPN11 cause metachondromatosis, but not ollier disease or Maffucci Syndrome
PLOS Genetics, 2011Co-Authors: Margot E. Bowen, Eric D. Boyden, Ingrid A. Holm, Belinda Campos-xavier, Luisa Bonafé, Andrea Superti-furga, Shiro Ikegawa, Valérie Cormier-daire, Twinkal C PansuriyaAbstract:Metachondromatosis (MC) is a rare, autosomal dominant, incompletely penetrant combined exostosis and enchondromatosis tumor Syndrome. MC is clinically distinct from other multiple exostosis or multiple enchondromatosis Syndromes and is unlinked to EXT1 and EXT2, the genes responsible for autosomal dominant multiple osteochondromas (MO). To identify a gene for MC, we performed linkage analysis with high-density SNP arrays in a single family, used a targeted array to capture exons and promoter sequences from the linked interval in 16 participants from 11 MC families, and sequenced the captured DNA using high-throughput parallel sequencing technologies. DNA capture and parallel sequencing identified heterozygous putative loss-of-function mutations in PTPN11 in 4 of the 11 families. Sanger sequence analysis of PTPN11 coding regions in a total of 17 MC families identified mutations in 10 of them (5 frameshift, 2 nonsense, and 3 splice-site mutations). Copy number analysis of sequencing reads from a second targeted capture that included the entire PTPN11 gene identified an additional family with a 15 kb deletion spanning exon 7 of PTPN11. Microdissected MC lesions from two patients with PTPN11 mutations demonstrated loss-of-heterozygosity for the wild-type allele. We next sequenced PTPN11 in DNA samples from 54 patients with the multiple enchondromatosis disorders Ollier disease or Maffucci Syndrome, but found no coding sequence PTPN11 mutations. We conclude that heterozygous loss-of-function mutations in PTPN11 are a frequent cause of MC, that lesions in patients with MC appear to arise following a ‘‘second hit,’’ that MC may be locus heterogeneous since 1 familial and 5 sporadically occurring cases lacked obvious disease-causing PTPN11 mutations, and that PTPN11 mutations are not a common cause of Ollier disease or Maffucci Syndrome.
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3 o 10 incidence predictive factors and prognosis of central chondrosarcoma in patients with ollier disease and Maffucci Syndrome report of 133 patients
Journal of Bone and Joint Surgery-british Volume, 2010Co-Authors: Suzan Hm Verdegaal, Judith V.m.g. Bovée, Twinkal C Pansuriya, Robert J Grimer, B Toker, Paul C Jutte, San M Julian, David Biau, I C M Van Der Geest, Andreas LeithnerAbstract:Enchondromatosis is a non-hereditary disease, characterised by the presence of multiple enchondromas. While Ollier Disease is typified by multiple enchondromas, in Maffucci Syndrome they are combined with haemangioma. Due to the rarity of these diseases, systematic studies on clinical behaviour providing information how to treat patients are lacking. This study intends to answer the following questions: What are predictive factors for developing chondrosarcoma? When is extensive surgery necessary? How often patients die due to dedifferentiation or metastasis? Twelve institutes in eight countries participated in this descriptive retrospective EMSOS-study. 118 Patients with Ollier Disease and 15 patients with Maffucci Syndrome were included. Unilateral localization of disease was found in 60% of Ollier patients and 40% of patients with Maffucci Syndrome. One of the predictive factors for developing chondrosarcoma is the location of the enchondromas; the risk increases especially when enchondromas are located in the scapula (33%), humerus (18%), pelvis (26%) or femur (15%). For the phalanges, this risk is 14% in the hand and 16% in the feet. The decision whether or not to perform extensive surgery is difficult, especially in patients who suffer multiple chondrosarcomas. Malignant transformation was found in fourty-four patients with Ollier Disease (37%) and eight patients with Maffucci Syndrome (53%). Multiple synchronous or metachronous chondrosarcomas were found in 15 patients. Nine patients died (range 21–54 yrs). Seven of them died disease related due to pulmonary metastasis (2 humerus, 2 pelvis, 3 femur). Two patients died from glioma of the brain. In conclusion, one important predictive factor for developing chondrosarcoma is the location of the enchondromas; interestingly, only patients with chondrosarcoma outside the small bones died of their disease. In this series, no dedifferentiation of chondrosarcoma was seen. A first design flow-chart how to approach chondrosarcoma in patients with Ollier Disease and Maffucci Syndrome is in preparation.
Zhengping Zhuang - One of the best experts on this subject based on the ideXlab platform.
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somatic idh1 mutation in a pituitary adenoma of a patient with Maffucci Syndrome
Journal of Neurosurgery, 2016Co-Authors: Christopher S Hong, Chunzhang Yang, Prashant Chittiboina, Junting Zhang, Jie Feng, Zhengping ZhuangAbstract:Maffucci Syndrome is a rare disease characterized by multiple enchondromas and soft-tissue hemangiomas. Additionally, neuroendocrine tumors including pituitary adenomas have been described in these patients. The underlying genetic etiology lies in somatic mosaicism of mutations in isocitrate dehydrogenase 1 (IDH1) or isocitrate dehydrogenase 2 (IDH2). This report describes a patient with Maffucci Syndrome who presented with intracranial tumors of the skull base and suprasellar region. The patient underwent resection of both intracranial tumors, revealing histopathological diagnoses of chondrosarcoma and pituitary adenoma. DNA sequencing of the tumors was performed to identify common IDH1/2 mutations. Clinical, radiological, and biochemical assessments were performed. Genotypic studies used standard Sanger sequencing in conjunction with a target-specific peptide nucleic acid to detect IDH1 mutations in tumor tissues. DNA sequencing demonstrated identical IDH1 mutations (c.394C > T) in both tumors. To the a...
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somatic idh1 mutation in a pituitary adenoma of a patient with Maffucci Syndrome
Journal of Neurosurgery, 2016Co-Authors: Shuyu Hao, Chunzhang Yang, Prashant Chittiboina, Christopher S Hong, Junting Zhang, Jie Feng, Zhengping ZhuangAbstract:Maffucci Syndrome is a rare disease characterized by multiple enchondromas and soft-tissue hemangiomas. Additionally, neuroendocrine tumors including pituitary adenomas have been described in these patients. The underlying genetic etiology lies in somatic mosaicism of mutations in isocitrate dehydrogenase 1 (IDH1) or isocitrate dehydrogenase 2 (IDH2). This report describes a patient with Maffucci Syndrome who presented with intracranial tumors of the skull base and suprasellar region. The patient underwent resection of both intracranial tumors, revealing histopathological diagnoses of chondrosarcoma and pituitary adenoma. DNA sequencing of the tumors was performed to identify common IDH1/2 mutations. Clinical, radiological, and biochemical assessments were performed. Genotypic studies used standard Sanger sequencing in conjunction with a target-specific peptide nucleic acid to detect IDH1 mutations in tumor tissues. DNA sequencing demonstrated identical IDH1 mutations (c.394C > T) in both tumors. To the authors' knowledge, this report provides the first genetic evidence for the inclusion of pituitary adenomas among tumors characterizing Maffucci Syndrome. In patients who are newly diagnosed with Maffucci Syndrome, it is appropriate to monitor for development of pituitary pathology and neuroendocrine dysfunction.
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ge 01idh1 mutated pituitary adenoma challenges traditional characterization of Maffucci Syndrome
Neuro-oncology, 2015Co-Authors: Christopher S Hong, Chunzhang Yang, Prashant Chittiboina, Junting Zhang, Jie Feng, Shuyu Hao, Zhengping ZhuangAbstract:Maffucci Syndrome is a rare, non-inheritable condition of mesodermal dysplasia, presenting in childhood with formation of multiple enchondromas and soft-tissue hemangiomas. Approximately, 40% of enchondromas undergo malignant transformation into chondrosarcomas. The underlying genetic etiology lies in somatic mosaicism of mutations in isocitrate dehydrogenase 1 (IDH1) or IDH2, which have been detected simultaneously in both tumors and blood leukocytes of affected patients. We describe a 7-year old male who presented with extensive enchondromatosis and subcutaneous hemangiomas, clinically diagnosed as Maffucci Syndrome. Years later, he developed sub-acute dysphasia, dysarthria, and loss of left visual acuity. A brain MRI demonstrated two heterogeneously enhancing lesions, one centered in the left jugular foramen and the other located in the supra-sellar region. Surgical resections of both intracranial tumors were performed over a period of ten months. Histopathological review revealed diagnoses of a grade II chondrosarcoma as well as a non-functional pituitary adenoma after subsequent neuroendocrine studies were unremarkable. Genotypic studies of the tumors were performed to identify common IDH1/2 mutations. DNA sequencing utilized standard Sanger sequencing in conjunction with a target-specific peptide nucleic acid (PNA) to detect IDH1 mutations in tumor tissues. The results demonstrated identical IDH1 mutations (c.394C > T; R132C) in both tumors. This result represents the first genetic evidence to establish causality between pituitary adenoma formation and tumor predisposition in Maffucci Syndrome. As neuro-ectodermal tissue, this IDH1-mutated pituitary adenoma challenges the notion that Maffucci Syndrome only involves mesodermal tissues. As such, in pediatric patients newly diagnosed with Maffucci Syndrome, it may be appropriate to monitor for development of pituitary pathology and neuroendocrine dysfunction. Conversely, in the rare sub-population of pediatric neuro-oncology patients with concomitant non-nervous system tumors, further investigation is warranted to rule out Maffucci Syndrome, as there may be considerable risk for malignant transformation as well as additional tumor formation.
Suzan Hm Verdegaal - One of the best experts on this subject based on the ideXlab platform.
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incidence predictive factors and prognosis of chondrosarcoma in patients with ollier disease and Maffucci Syndrome an international multicenter study of 161 patients
Oncologist, 2011Co-Authors: Suzan Hm Verdegaal, Twinkal C Pansuriya, Robert J Grimer, Paul C Jutte, David Biau, I C M Van Der Geest, Harzem Ozger, Mikel San Julian, Andreas LeithnerAbstract:Background. Enchondromatosis is characterized by the presence of multiple benign cartilage lesions in bone. While Ollier disease is typified by multiple enchondromas, in Maffucci Syndrome these are associated with hemangiomas. Studies evaluating the predictive value of clinical symptoms for development of secondary chondrosarcoma and prognosis are lacking. This multi-institute study evaluates the clinical characteristics of patients, to get better insight on behavior and prognosis of these diseases. Method.Aretrospectivestudywasconductedusingclinical dataof144Ollierand17Maffuccipatientsfrom13European centers and one national databank supplied by members of the European Musculoskeletal Oncology Society. Results. Patients had multiple enchondromas in the hands and feet only (group I, 18%), in long bones including scapula and pelvis only (group II, 39%), and in both small and long/flat bones (group III, 43%), respectively. The overall incidence of chondrosarcoma thus far is 40%. In group I, only 4 patients (15%) developed chondrosarcoma, in contrast to 27 patients (43%) in group II and 26 patients (46%) in group III, respectively. The risk of developing chondrosarcoma is increased when enchondromas are located in the pelvis (odds ratio, 3.8; p 0.00l). Conclusions. Overall incidence of development of chondrosarcoma is 40%, but may, due to age-dependency, increase when considered as a lifelong risk. Patients with
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Maffucci Syndrome a genome wide analysis using high resolution single nucleotide polymorphism and expression arrays on four cases
Genes Chromosomes and Cancer, 2011Co-Authors: Twinkal C Pansuriya, Jan Oosting, Suzan Hm Verdegaal, Pancras Cw Hogendoorn, Raf Sciot, Adrienne M Flanagan, Larsgunnar Kindblom, Karoly Szuhai, Judith V.m.g. BovéeAbstract:Ollier disease and Maffucci Syndrome are rare, nonhereditary skeletal disorders characterized by the presence of multiple enchondromas with (Maffucci) or without (Ollier) co-existing multiple hemangiomas of soft tissue. Enchondromas can progress toward central chondrosarcomas. PTH1R mutations are found in a small subset of Ollier patients. The genetic deficit in Maffucci Syndrome is unknown. Here, we report the first genome-wide analysis using Affymetrix SNP 6.0 array on Maffucci enchondromas (n = 4) and chondrosarcomas (n = 2) from four cases. Results were compared to a previously studied cohort of Ollier patients (n = 37). We found no loss of heterozygosity (LOH) or common copy number alterations shared by all enchondromas, with the exception of some copy number variations. As expected, chondrosarcomas were found to have multiple genomic imbalances. This is similar to conventional solitary and Ollier-related enchondromas and chondrosarcomas and supports the multistep genetic progression model. Expression profiling using Illumina BeadArray-v3 chip revealed that cartilaginous tumors in Maffucci patients are more similar to such tumors in Ollier patients than to sporadic cartilage tumors. Point mutations in a single gene or other copy number neutral genomic changes might play a role in enchondromagenesis.
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3 o 10 incidence predictive factors and prognosis of central chondrosarcoma in patients with ollier disease and Maffucci Syndrome report of 133 patients
Journal of Bone and Joint Surgery-british Volume, 2010Co-Authors: Suzan Hm Verdegaal, Judith V.m.g. Bovée, Twinkal C Pansuriya, Robert J Grimer, B Toker, Paul C Jutte, San M Julian, David Biau, I C M Van Der Geest, Andreas LeithnerAbstract:Enchondromatosis is a non-hereditary disease, characterised by the presence of multiple enchondromas. While Ollier Disease is typified by multiple enchondromas, in Maffucci Syndrome they are combined with haemangioma. Due to the rarity of these diseases, systematic studies on clinical behaviour providing information how to treat patients are lacking. This study intends to answer the following questions: What are predictive factors for developing chondrosarcoma? When is extensive surgery necessary? How often patients die due to dedifferentiation or metastasis? Twelve institutes in eight countries participated in this descriptive retrospective EMSOS-study. 118 Patients with Ollier Disease and 15 patients with Maffucci Syndrome were included. Unilateral localization of disease was found in 60% of Ollier patients and 40% of patients with Maffucci Syndrome. One of the predictive factors for developing chondrosarcoma is the location of the enchondromas; the risk increases especially when enchondromas are located in the scapula (33%), humerus (18%), pelvis (26%) or femur (15%). For the phalanges, this risk is 14% in the hand and 16% in the feet. The decision whether or not to perform extensive surgery is difficult, especially in patients who suffer multiple chondrosarcomas. Malignant transformation was found in fourty-four patients with Ollier Disease (37%) and eight patients with Maffucci Syndrome (53%). Multiple synchronous or metachronous chondrosarcomas were found in 15 patients. Nine patients died (range 21–54 yrs). Seven of them died disease related due to pulmonary metastasis (2 humerus, 2 pelvis, 3 femur). Two patients died from glioma of the brain. In conclusion, one important predictive factor for developing chondrosarcoma is the location of the enchondromas; interestingly, only patients with chondrosarcoma outside the small bones died of their disease. In this series, no dedifferentiation of chondrosarcoma was seen. A first design flow-chart how to approach chondrosarcoma in patients with Ollier Disease and Maffucci Syndrome is in preparation.
Judith V.m.g. Bovée - One of the best experts on this subject based on the ideXlab platform.
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Maffucci Syndrome a genome wide analysis using high resolution single nucleotide polymorphism and expression arrays on four cases
Genes Chromosomes and Cancer, 2011Co-Authors: Twinkal C Pansuriya, Jan Oosting, Suzan Hm Verdegaal, Pancras Cw Hogendoorn, Raf Sciot, Adrienne M Flanagan, Larsgunnar Kindblom, Karoly Szuhai, Judith V.m.g. BovéeAbstract:Ollier disease and Maffucci Syndrome are rare, nonhereditary skeletal disorders characterized by the presence of multiple enchondromas with (Maffucci) or without (Ollier) co-existing multiple hemangiomas of soft tissue. Enchondromas can progress toward central chondrosarcomas. PTH1R mutations are found in a small subset of Ollier patients. The genetic deficit in Maffucci Syndrome is unknown. Here, we report the first genome-wide analysis using Affymetrix SNP 6.0 array on Maffucci enchondromas (n = 4) and chondrosarcomas (n = 2) from four cases. Results were compared to a previously studied cohort of Ollier patients (n = 37). We found no loss of heterozygosity (LOH) or common copy number alterations shared by all enchondromas, with the exception of some copy number variations. As expected, chondrosarcomas were found to have multiple genomic imbalances. This is similar to conventional solitary and Ollier-related enchondromas and chondrosarcomas and supports the multistep genetic progression model. Expression profiling using Illumina BeadArray-v3 chip revealed that cartilaginous tumors in Maffucci patients are more similar to such tumors in Ollier patients than to sporadic cartilage tumors. Point mutations in a single gene or other copy number neutral genomic changes might play a role in enchondromagenesis.
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3 o 10 incidence predictive factors and prognosis of central chondrosarcoma in patients with ollier disease and Maffucci Syndrome report of 133 patients
Journal of Bone and Joint Surgery-british Volume, 2010Co-Authors: Suzan Hm Verdegaal, Judith V.m.g. Bovée, Twinkal C Pansuriya, Robert J Grimer, B Toker, Paul C Jutte, San M Julian, David Biau, I C M Van Der Geest, Andreas LeithnerAbstract:Enchondromatosis is a non-hereditary disease, characterised by the presence of multiple enchondromas. While Ollier Disease is typified by multiple enchondromas, in Maffucci Syndrome they are combined with haemangioma. Due to the rarity of these diseases, systematic studies on clinical behaviour providing information how to treat patients are lacking. This study intends to answer the following questions: What are predictive factors for developing chondrosarcoma? When is extensive surgery necessary? How often patients die due to dedifferentiation or metastasis? Twelve institutes in eight countries participated in this descriptive retrospective EMSOS-study. 118 Patients with Ollier Disease and 15 patients with Maffucci Syndrome were included. Unilateral localization of disease was found in 60% of Ollier patients and 40% of patients with Maffucci Syndrome. One of the predictive factors for developing chondrosarcoma is the location of the enchondromas; the risk increases especially when enchondromas are located in the scapula (33%), humerus (18%), pelvis (26%) or femur (15%). For the phalanges, this risk is 14% in the hand and 16% in the feet. The decision whether or not to perform extensive surgery is difficult, especially in patients who suffer multiple chondrosarcomas. Malignant transformation was found in fourty-four patients with Ollier Disease (37%) and eight patients with Maffucci Syndrome (53%). Multiple synchronous or metachronous chondrosarcomas were found in 15 patients. Nine patients died (range 21–54 yrs). Seven of them died disease related due to pulmonary metastasis (2 humerus, 2 pelvis, 3 femur). Two patients died from glioma of the brain. In conclusion, one important predictive factor for developing chondrosarcoma is the location of the enchondromas; interestingly, only patients with chondrosarcoma outside the small bones died of their disease. In this series, no dedifferentiation of chondrosarcoma was seen. A first design flow-chart how to approach chondrosarcoma in patients with Ollier Disease and Maffucci Syndrome is in preparation.
Christopher S Hong - One of the best experts on this subject based on the ideXlab platform.
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somatic idh1 mutation in a pituitary adenoma of a patient with Maffucci Syndrome
Journal of Neurosurgery, 2016Co-Authors: Christopher S Hong, Chunzhang Yang, Prashant Chittiboina, Junting Zhang, Jie Feng, Zhengping ZhuangAbstract:Maffucci Syndrome is a rare disease characterized by multiple enchondromas and soft-tissue hemangiomas. Additionally, neuroendocrine tumors including pituitary adenomas have been described in these patients. The underlying genetic etiology lies in somatic mosaicism of mutations in isocitrate dehydrogenase 1 (IDH1) or isocitrate dehydrogenase 2 (IDH2). This report describes a patient with Maffucci Syndrome who presented with intracranial tumors of the skull base and suprasellar region. The patient underwent resection of both intracranial tumors, revealing histopathological diagnoses of chondrosarcoma and pituitary adenoma. DNA sequencing of the tumors was performed to identify common IDH1/2 mutations. Clinical, radiological, and biochemical assessments were performed. Genotypic studies used standard Sanger sequencing in conjunction with a target-specific peptide nucleic acid to detect IDH1 mutations in tumor tissues. DNA sequencing demonstrated identical IDH1 mutations (c.394C > T) in both tumors. To the a...
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somatic idh1 mutation in a pituitary adenoma of a patient with Maffucci Syndrome
Journal of Neurosurgery, 2016Co-Authors: Shuyu Hao, Chunzhang Yang, Prashant Chittiboina, Christopher S Hong, Junting Zhang, Jie Feng, Zhengping ZhuangAbstract:Maffucci Syndrome is a rare disease characterized by multiple enchondromas and soft-tissue hemangiomas. Additionally, neuroendocrine tumors including pituitary adenomas have been described in these patients. The underlying genetic etiology lies in somatic mosaicism of mutations in isocitrate dehydrogenase 1 (IDH1) or isocitrate dehydrogenase 2 (IDH2). This report describes a patient with Maffucci Syndrome who presented with intracranial tumors of the skull base and suprasellar region. The patient underwent resection of both intracranial tumors, revealing histopathological diagnoses of chondrosarcoma and pituitary adenoma. DNA sequencing of the tumors was performed to identify common IDH1/2 mutations. Clinical, radiological, and biochemical assessments were performed. Genotypic studies used standard Sanger sequencing in conjunction with a target-specific peptide nucleic acid to detect IDH1 mutations in tumor tissues. DNA sequencing demonstrated identical IDH1 mutations (c.394C > T) in both tumors. To the authors' knowledge, this report provides the first genetic evidence for the inclusion of pituitary adenomas among tumors characterizing Maffucci Syndrome. In patients who are newly diagnosed with Maffucci Syndrome, it is appropriate to monitor for development of pituitary pathology and neuroendocrine dysfunction.
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ge 01idh1 mutated pituitary adenoma challenges traditional characterization of Maffucci Syndrome
Neuro-oncology, 2015Co-Authors: Christopher S Hong, Chunzhang Yang, Prashant Chittiboina, Junting Zhang, Jie Feng, Shuyu Hao, Zhengping ZhuangAbstract:Maffucci Syndrome is a rare, non-inheritable condition of mesodermal dysplasia, presenting in childhood with formation of multiple enchondromas and soft-tissue hemangiomas. Approximately, 40% of enchondromas undergo malignant transformation into chondrosarcomas. The underlying genetic etiology lies in somatic mosaicism of mutations in isocitrate dehydrogenase 1 (IDH1) or IDH2, which have been detected simultaneously in both tumors and blood leukocytes of affected patients. We describe a 7-year old male who presented with extensive enchondromatosis and subcutaneous hemangiomas, clinically diagnosed as Maffucci Syndrome. Years later, he developed sub-acute dysphasia, dysarthria, and loss of left visual acuity. A brain MRI demonstrated two heterogeneously enhancing lesions, one centered in the left jugular foramen and the other located in the supra-sellar region. Surgical resections of both intracranial tumors were performed over a period of ten months. Histopathological review revealed diagnoses of a grade II chondrosarcoma as well as a non-functional pituitary adenoma after subsequent neuroendocrine studies were unremarkable. Genotypic studies of the tumors were performed to identify common IDH1/2 mutations. DNA sequencing utilized standard Sanger sequencing in conjunction with a target-specific peptide nucleic acid (PNA) to detect IDH1 mutations in tumor tissues. The results demonstrated identical IDH1 mutations (c.394C > T; R132C) in both tumors. This result represents the first genetic evidence to establish causality between pituitary adenoma formation and tumor predisposition in Maffucci Syndrome. As neuro-ectodermal tissue, this IDH1-mutated pituitary adenoma challenges the notion that Maffucci Syndrome only involves mesodermal tissues. As such, in pediatric patients newly diagnosed with Maffucci Syndrome, it may be appropriate to monitor for development of pituitary pathology and neuroendocrine dysfunction. Conversely, in the rare sub-population of pediatric neuro-oncology patients with concomitant non-nervous system tumors, further investigation is warranted to rule out Maffucci Syndrome, as there may be considerable risk for malignant transformation as well as additional tumor formation.
