Brain Tumors, IDH2

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Expand Collapse Brain Tumors  - General Description Data summarized by the CBTRUS (the Central Brain Tumor Registry of the United States) Statistical Report: Primary Brain and Central Nervous System Tumors diagnosed in the U.S. between 2008 and 2012 was analyzed and published in 2015. It includes malignant and non-malignant tumors in brain, meninges, spinal cord, cranial nerves, and other parts of the central nervous system, pituitary and pineal glands, and olfactory tumors of the nasal cavity. In the 2015 published report, the final number of all newly diagnosed tumors including all of the above was 356,858 in the U.S. between 2008 and 2012. The most commonly diagnosed CNS tumors are meningiomas (36.4% for this time period), followed by tumors of the pituitary (15.5% for this time period). Gliomas are tumors that arise from glial or precursor cells in the CNS, and include glioblastoma (15.1% for this time period), astrocytoma, oligodendroglioma, ependymoma, mixed glioma and malignant glioma, and a few other rare histologies. Of the 356,858 tumors included in the CBTRUS 2015 analysis, 239,835 (67.2%) were non-malignant tumors, while 117,023 of the CNS tumors for this time period were malignant.
Few definitive observations on environmental or occupational causes of primary Central Nervous System (CNS) tumors have been made. The following risk factors have been considered: Exposure to vinyl chloride may be a risk factor for glioma. Radiation exposure is a risk factor for meningioma. Epstein-Barr virus infection has been implicated in the etiology of primary CNS lymphoma. Transplant recipients and patients with the acquired immunodeficiency syndrome have substantially increased risks for primary CNS lymphoma.
Familial tumor syndromes and related chromosomal abnormalities that are associated with CNS neoplasms include the following: Neurofibromatosis type I (17q11), neurofibromatosis type II (22q12), von Hippel-Lindau disease (3p25-26), tuberous sclerosis complex (9q34, 16p13), Li-Fraumeni syndrome (17p13), Turcot syndrome type 1 (3p21, 7p22), Turcot syndrome type 2 (5q21), nevoid basal cell carcinoma syndrome (9q22.3) and multiple endocrine neoplasia type 1 (11q13).

Sources: National Cancer Institute, 2016
CBTRUS Statistical Report: Primary Brain and CNS Tumors Diagnosed in the US in 2008-2012; Neuro Oncol; 2015


Data summarized by the CBTRUS (the Central Brain Tumor Registry of the United States) Statistical Report: Primary Brain and Central Nervous System Tumors diagnosed in the U.S. between 2008 and 2012 was analyzed and published in 2015. It includes malignant and non-malignant tumors in brain, meninges, spinal cord, cranial nerves, and other parts of the central nervous system, pituitary and pineal glands, and olfactory tumors of the nasal cavity. In the 2015 published report, the final number of all newly diagnosed tumors including all of the above was 356,858 in the U.S. between 2008 and 2012. The most commonly diagnosed CNS tumors are meningiomas (36.4% for this time period), followed by tumors of the pituitary (15.5% for this time period). Gliomas are tumors that arise from glial or precursor cells in the CNS, and include glioblastoma (15.1% for this time period), astrocytoma, oligodendroglioma, ependymoma, mixed glioma and malignant glioma, and a few other rare histologies. Of the 356,858 tumors included in the CBTRUS 2015 analysis, 239,835 (67.2%) were non-malignant tumors, while 117,023 of the CNS tumors for this time period were malignant.
Few definitive observations on environmental or occupational causes of primary Central Nervous System (CNS) tumors have been made. The following risk factors have been considered: Exposure to vinyl chloride may be a risk factor for glioma. Radiation exposure is a risk factor for meningioma. Epstein-Barr virus infection has been implicated in the etiology of primary CNS lymphoma. Transplant recipients and patients with the acquired immunodeficiency syndrome have substantially increased risks for primary CNS lymphoma.
Familial tumor syndromes and related chromosomal abnormalities that are associated with CNS neoplasms include the following: Neurofibromatosis type I (17q11), neurofibromatosis type II (22q12), von Hippel-Lindau disease (3p25-26), tuberous sclerosis complex (9q34, 16p13), Li-Fraumeni syndrome (17p13), Turcot syndrome type 1 (3p21, 7p22), Turcot syndrome type 2 (5q21), nevoid basal cell carcinoma syndrome (9q22.3) and multiple endocrine neoplasia type 1 (11q13).

Sources: National Cancer Institute, 2016
CBTRUS Statistical Report: Primary Brain and CNS Tumors Diagnosed in the US in 2008-2012; Neuro Oncol; 2015


Data summarized by the CBTRUS (the Central Brain Tumor Registry of the United States) Statistical Report: Primary Brain and Central Nervous System Tumors diagnosed in the U.S. between 2008 and 2012 was analyzed and published in 2015. It includes malignant and non-malignant tumors in brain, meninges, spinal cord, cranial nerves, and other parts of the central nervous system, pituitary and pineal glands, and olfactory tumors of the nasal cavity. In the 2015 published report, the final number of all newly diagnosed tumors including all of the above was 356,858 in the U.S. between 2008 and 2012. The most commonly diagnosed CNS tumors are meningiomas (36.4% for this time period), followed by tumors of the pituitary (15.5% for this time period). Gliomas are tumors that arise from glial or precursor cells in the CNS, and include glioblastoma (15.1% for this time period), astrocytoma, oligodendroglioma, ependymoma, mixed glioma and malignant glioma, and a few other rare histologies. Of the 356,858 tumors included in the CBTRUS 2015 analysis, 239,835 (67.2%) were non-malignant tumors, while 117,023 of the CNS tumors for this time period were malignant.
Few definitive observations on environmental or occupational causes of primary Central Nervous System (CNS) tumors have been made. The following risk factors have been considered: Exposure to vinyl chloride may be a risk factor for glioma. Radiation exposure is a risk factor for meningioma. Epstein-Barr virus infection has been implicated in the etiology of primary CNS lymphoma. Transplant recipients and patients with the acquired immunodeficiency syndrome have substantially increased risks for primary CNS lymphoma.
Familial tumor syndromes and related chromosomal abnormalities that are associated with CNS neoplasms include the following: Neurofibromatosis type I (17q11), neurofibromatosis type II (22q12), von Hippel-Lindau disease (3p25-26), tuberous sclerosis complex (9q34, 16p13), Li-Fraumeni syndrome (17p13), Turcot syndrome type 1 (3p21, 7p22), Turcot syndrome type 2 (5q21), nevoid basal cell carcinoma syndrome (9q22.3) and multiple endocrine neoplasia type 1 (11q13).

Sources: National Cancer Institute, 2016
CBTRUS Statistical Report: Primary Brain and CNS Tumors Diagnosed in the US in 2008-2012; Neuro Oncol; 2015


Data summarized by the CBTRUS (the Central Brain Tumor Registry of the United States) Statistical Report: Primary Brain and Central Nervous System Tumors diagnosed in the U.S. between 2008 and 2012 was analyzed and published in 2015. It includes malignant and non-malignant tumors in brain, meninges, spinal cord, cranial nerves, and other parts of the central nervous system, pituitary and pineal glands, and olfactory tumors of the nasal cavity. In the 2015 published report, the final number of all newly diagnosed tumors including all of the above was 356,858 in the U.S. between 2008 and 2012. The most commonly diagnosed CNS tumors are meningiomas (36.4% for this time period), followed by tumors of the pituitary (15.5% for this time period). Gliomas are tumors that arise from glial or precursor cells in the CNS, and include glioblastoma (15.1% for this time period), astrocytoma, oligodendroglioma, ependymoma, mixed glioma and malignant glioma, and a few other rare histologies. Of the 356,858 tumors included in the CBTRUS 2015 analysis, 239,835 (67.2%) were non-malignant tumors, while 117,023 of the CNS tumors for this time period were malignant.
Few definitive observations on environmental or occupational causes of primary Central Nervous System (CNS) tumors have been made. The following risk factors have been considered: Exposure to vinyl chloride may be a risk factor for glioma. Radiation exposure is a risk factor for meningioma. Epstein-Barr virus infection has been implicated in the etiology of primary CNS lymphoma. Transplant recipients and patients with the acquired immunodeficiency syndrome have substantially increased risks for primary CNS lymphoma.
Familial tumor syndromes and related chromosomal abnormalities that are associated with CNS neoplasms include the following: Neurofibromatosis type I (17q11), neurofibromatosis type II (22q12), von Hippel-Lindau disease (3p25-26), tuberous sclerosis complex (9q34, 16p13), Li-Fraumeni syndrome (17p13), Turcot syndrome type 1 (3p21, 7p22), Turcot syndrome type 2 (5q21), nevoid basal cell carcinoma syndrome (9q22.3) and multiple endocrine neoplasia type 1 (11q13).

Sources: National Cancer Institute, 2016
CBTRUS Statistical Report: Primary Brain and CNS Tumors Diagnosed in the US in 2008-2012; Neuro Oncol; 2015


Expand Collapse IDH2  - General Description
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Isocitrate dehydrogenase 2, encoded by the IDH2 gene, is an enzyme found in the powerhouse of the cells, known as mitochondria. This enzyme is similar to IDH1 in that it is involved in the transfer of energy from one molecule to another during certain biochemical reactions.

Mutations in IDH2 are predominately found in patients with acute myeloid leukemia, cancer of the bile duct (cholangiocarcinoma) and certain soft tissue tumors (sarcoma), and are found less frequently in patients with cancers of the central nervous system. Cancer mutations in the IDH2 gene primarily cause the amino acid arginine to be replaced by a different amino acid at the 140th or 172nd position in this protein. The change in sequence alters the structure of the protein, which results in loss of the normal enzymatic function of IDH2. Instead of producing its normal end-product (alpha-ketoglutarate), it produces the new metabolite R(-)-2-hydroxyglutarate (2HG), which is thought to contribute directly to the tumorigenic process by altering the activity of a number of proteins. The net effect is the inability to express a number of genes and the ability to activate signaling pathways involved in metabolism, and growth of new tumor vasculature.

The highest incidence of IDH2 gene mutations have been reported in acute myeloid leukemia (5-20%), cholangiocarcinoma (4-6%), and central cartilaginous tumors (~5%).
The IDH2 gene encodes for the metabolic enzyme isocitrate dehydrogenase 2. Unlike IDH1, IDH2 is localized within the mitochondria. While IDH2 functions similarly to IDH1 by catalyzing the oxidative decarboxylation of isocitrate to alpha-ketoglutarate, NAD+ is the final electron acceptor, thereby producing NADH.

Somatic mutations in IDH2 are found most frequently in acute myeloid leukemia, bile duct tumors (cholangiocarcinoma) and certain sarcomas, and to a much lesser extent in low-grade gliomas and secondary glioblastomas. These mutations result in decreased normal enzymatic activity and result in the neomorphic activity of producing the oncometabolite R(-)-2-hydroxyglutarate (2HG) as the end-product. Levels of 2HG can accumulate dramatically in IDH2-mutant tumors and this is thought to promote tumorigenesis by competitively inhibiting the activity of a number of dioxygenases. The net effect appears to involve the promotion of gene silencing through hypermethylation of DNA and histones, as well as the activation of the hypoxia-inducible factor signaling pathway.

The highest incidence of IDH2 gene mutations have been reported in acute myeloid leukemia (5-20%), cholangiocarcinoma (4-6%), and central cartilaginous tumors (~5%).
PubMed ID's
22234630, 22180306, 20884716, 21598255
Expand Collapse IDH2  in Brain Tumors
IDH2 mutations, while rare in glioma, predominately occur in oligodendroglial tumors and are associated with 1p/19q codeletion.

The novel enzymatic activity conferred by IDH2 gene mutations in cancer is believed to provide a robust target for therapeutic intervention. However, therapies that target mutant IDH activity are still under active development and have not yet reached clinical trial testing.

The chance that a particular glioma tumor will carry an IDH2 mutation is more than 20 times less likely than it carrying an IDH1 mutation. Therefore, the implications of IDH2 mutations in glioma have not been as well characterized as those for IDH1. However, the best evidence suggests that IDH2 is also associated with a significantly younger age and a significantly better prognosis when compared to patients carrying normal IDH2 (IDH2 wild-type).

IDH2 mutations, while rare in glioma, predominately occur in oligodendroglial tumors and are associated with 1p/19q codeletion.

The novel enzymatic activity conferred by IDH2 gene mutations in cancer is believed to provide a robust target for therapeutic intervention. However, therapies that target mutant IDH activity are still under active development and have not yet reached clinical trial testing.

The chance that a particular glioma tumor will carry an IDH2 mutation is more than 20 times less likely than it carrying an IDH1 mutation. Therefore, the implications of IDH2 mutations in glioma have not been as well characterized as those for IDH1. However, the best evidence suggests that IDH2 is also associated with a significantly younger age and a significantly better prognosis when compared to patients carrying normal IDH2 (IDH2 wild-type).

PubMed ID's
19228619, 19554337, 20427748, 20975057
Expand Collapse No mutation selected
The mutation of a gene provides clinicians with a very detailed look at your cancer. Knowing this information could change the course of your care. To learn how you can find out more about genetic testing please visit http://www.massgeneral.org/cancer/news/faq.aspx or contact the Cancer Center.
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Your Matched Clinical Trials

Trial Matches: (D) - Disease, (G) - Gene
Trial Status: Showing all 7 results Per Page:
Protocol # Title Location Status Match
NCT02101736 Cabozantinib for Plexiform Neurofibromas (PN) in Subjects With NF1 in Children and Adults Cabozantinib for Plexiform Neurofibromas (PN) in Subjects With NF1 in Children and Adults MGH Open D
NCT02179086 Dose-Escalated Photon IMRT or Proton Beam Radiation Therapy Versus Standard-Dose Radiation Therapy and Temozolomide in Treating Patients With Newly Diagnosed Glioblastoma Dose-Escalated Photon IMRT or Proton Beam Radiation Therapy Versus Standard-Dose Radiation Therapy and Temozolomide in Treating Patients With Newly Diagnosed Glioblastoma MGH Open D
NCT01849952 Evaluating the Expression Levels of MicroRNA-10b in Patients With Gliomas Evaluating the Expression Levels of MicroRNA-10b in Patients With Gliomas MGH Open D
NCT01228448 In-Room PET in Proton Radiation Therapy In-Room PET in Proton Radiation Therapy MGH Open D
NCT02525692 Oral ONC201 in Recurrent GBM, H3 K27M Glioma, and Midline Glioma Oral ONC201 in Recurrent GBM, H3 K27M Glioma, and Midline Glioma MGH Open D
NCT02112617 Phase II Study of Proton Radiation Therapy for Neuroblastoma Phase II Study of Proton Radiation Therapy for Neuroblastoma MGH Open D
NCT02176967 Response and Biology-Based Risk Factor-Guided Therapy in Treating Younger Patients With Non-high Risk Neuroblastoma Response and Biology-Based Risk Factor-Guided Therapy in Treating Younger Patients With Non-high Risk Neuroblastoma MGH Open D
MGH has many open clinical trials for other cancers not shown on the Targeted Cancer Care website. They can be found on the MassGeneral.org clinical trials search page.

Additional clinical trials may be applicable to your search criteria, but they may not be available at MGH. These clinical trials can typically be found by searching the clinicaltrials.gov website.
Trial Status: Showing all 7 results Per Page:
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