Brain Tumors, NF2, all inactivating mutations

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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 NF2  - General Description
The NF2 gene encodes a protein called merlin, also known as schwannomin. This protein is produced in the nervous system, particularly in specialized cells called Schwann cells that wrap around and insulate nerves. Merlin is thought to play a role in controlling cell shape, cell movement, and communication between cells. To carry out these tasks, merlin associates with the internal framework that supports the cell, called the cytoskeleton. Merlin also functions as a tumor suppressor protein, which prevents cells from growing and dividing too fast or in an uncontrolled way.

Over 200 different mutations in the NF2 gene have been found in people who have Neurofibromatosis type 2. Most of these mutations result in abnormally shortened versions of the merlin protein, which no longer can perform its normal role as a tumor suppressor in cells. Loss of the normal version of merlin allows Schwann cells to multiply too frequently and form non-cancerous tumors. The most common types of tumors in neurofibromatosis type 2 are tumors that develop along the nerve that carries information from the inner ear to the brain. Other types of tumors affecting the nervous system also occur in patients with this condition.

Other types of mutations in the NF2 gene are acquired during a person’s lifetime, and these somatic mutations are found only in certain cells. Somatic mutations in the NF2 gene have been found in noncancerous (benign) and cancerous (malignant) tumors in patients. Somatic mutations in the NF2 gene have been associated with a disorder called schwannomatosis, similar to neurofibromatosis type 2. This condition is characterized by the development of multiple non-cancerous tumors called schwannomas. These tumors may develop in nerves throughout the body, but not usually along the auditory nerve as in neurofibromatosis type 2. Researchers are not certain that the mutations in the NF2 gene are responsible for schwannomatosis, and are still looking for other genes that contribute to this condition.

Loss of or inactivation of the NF2 gene is associated with approximately 50% of a common type of brain or spinal cord tumor called a meningioma. These tumors arise from the meninges, the layers of tissue that cover and protect the brain and spinal cord. Although most meningiomas are benign, many can be associated with neurologic symptoms. A small percentage of meningiomas become malignant and have higher recurrence rates. Clinical trials are underway studying targeted therapies at MGH and in other centers to treat meningiomas (contact Regina Silver, 617-643-1939 at MGH for information).

Mesotheliomas are cancerous tumors that can arise in the lining of the lung and chest cavity (pleura) or in the lining of the abdomen (peritoneum). These aggressive tumors are often associated with exposure to asbestos. Researchers have determined that inactivation of the NF2 gene occurs in approximately half of all cases of mesothelioma.

Information from Genetic home reference 2016
www.tumorportal.org
NF2 neurofibromin 2 (merlin)
The NF2 gene encodes a protein called merlin, also known as schwannomin. This protein is made in the nervous system, particularly in specialized cells called Schwann cells that wrap around and insulate nerves. Merlin is similar to some members of the ERM (Ezrin, radixin, moesin) family of proteins that are thought to link cytoskeletal componenet with proteins in the cell membrane. This gene product has been shown to interact with cell-surface proteins, proteins involved in cytoskeletal dynamics and proteins involved in regulating ion transport. This gene is expressed at high levels during embryonic development; in adults, significant expression is found in Schwann cell, meningeal cells, lens and nerve. Mutations in this gene are associated with neurofibromatosis type II which is characterized by nervous system and skin tumors and ocular abnormalities. Two predominant isoforms and a number of minor isoforms are produced by alternatively spliced transcripts of the NF2 gene.

Over 200 different mutations in the NF2 gene have been found in people who have Neurofibromatosis type 2. Most of these mutations result in abnormally shortened versions of the merlin protein, which no longer can perform its normal role as a tumor suppressor in cells. Loss of the normal version of merlin allows Schwann cells to multiply too frequently and form non-cancerous tumors. The most common types of tumors in neurofibromatosis type 2 are tumors that develop along the nerve that carries information from the inner ear to the brain. Other types of tumors affecting the nervous system also occur in patients with this condition.
Other types of mutations in the NF2 gene are acquired during a person’s lifetime, and these somatic mutations are found only in certain cells. Somatic mutations in the NF2 gene have been found in noncancerous (benign) and cancerous (malignant) tumors in patients. Somatic mutations in the NF2 gene have been associated with a disorder called schwannomatosis, similar to neurofibromatosis type 2. This condition is characterized by the development of multiple non-cancerous tumors called schwannomas. These tumors may develop in nerves throughout the body, but not usually along the auditory nerve as in neurofibromatosis type 2. Researchers are not certain that the mutations in the NF2 gene are responsible for schwannomatosis, and are still looking for other genes that contribute to this condition.

Loss of or inactivation of the NF2 gene is associated with approximately 50% of a common type of brain or spinal cord tumor called a meningioma. These tumors arise from the meninges, the layers of tissue that cover and protect the brain and spinal cord. Although most meningiomas are benign, many can be associated with neurologic symptoms. A small percentage of meningiomas become malignant and have higher recurrence rates. Clinical trials are underway studying targeted therapies at MGH and in other centers to treat meningiomas (contact Regina Silver, 617-643-1939 at MGH for information).

Mesotheliomas are cancerous tumors that can arise in the lining of the lung and chest cavity (pleura) or in the lining of the abdomen (peritoneum). These aggressive tumors are often associated with exposure to asbestos. Researchers have determined that inactivation of the NF2 gene occurs in approximately half of all cases of mesothelioma.

Information from Genetic home reference 2016
www.tumorportal.org

PubMed ID's
23334667
Expand Collapse all inactivating mutations  in NF2
NF2 mutations associated with tumors inactivate NF2. These mutations render the protein unable to perform its normal function as a tumor suppressor.
NF2 mutations associated with tumors inactivate NF2. These mutations render the protein unable to perform its normal function as a tumor suppressor.

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Your Matched Clinical Trials

Trial Matches: (D) - Disease, (G) - Gene, (M) - Mutation
Trial Status: Showing Results: 1-10 of 14 Per Page:
12Next »
Protocol # Title Location Status Match
NCT02523014 A Study Looking at Targeted Therapy According to Tumor Markers for People With Meningiomas A Study Looking at Targeted Therapy According to Tumor Markers for People With Meningiomas MGH Open DGM
NCT02365662 A Study Evaluating Safety and Pharmacokinetics of ABBV-221 in Subjects With Advanced Solid Tumor Types Likely to Exhibit Elevated Levels of Epidermal Growth Factor Receptor A Study Evaluating Safety and Pharmacokinetics of ABBV-221 in Subjects With Advanced Solid Tumor Types Likely to Exhibit Elevated Levels of Epidermal Growth Factor Receptor MGH Open D
NCT02573324 A Study of ABT-414 in Subjects With Newly Diagnosed Glioblastoma (GBM) With Epidermal Growth Factor Receptor (EGFR) Amplification A Study of ABT-414 in Subjects With Newly Diagnosed Glioblastoma (GBM) With Epidermal Growth Factor Receptor (EGFR) Amplification MGH Open D
NCT02927340 A Study of Lorlatinib in Advanced ALK and ROS1 Rearranged Lung Cancer With CNS Metastasis in the Absence of Measurable Extracranial Lesions A Study of Lorlatinib in Advanced ALK and ROS1 Rearranged Lung Cancer With CNS Metastasis in the Absence of Measurable Extracranial Lesions MGH Open D
NCT01987830 Bevacizumab w / Temozolomide PET & Vascular MRI For GBM Bevacizumab w / Temozolomide PET & Vascular MRI For GBM MGH Open D
NCT01295944 Carboplatin and Bevacizumab for Recurrent Ependymoma Carboplatin and Bevacizumab for Recurrent Ependymoma MGH Open D
NCT02764151 First in Patient Study for PF-06840003 in Malignant Gliomas First in Patient Study for PF-06840003 in Malignant Gliomas MGH Open D
NCT02709889 Rovalpituzumab Tesirine in Delta-Like Protein 3-Expressing Advanced Solid Tumors Rovalpituzumab Tesirine in Delta-Like Protein 3-Expressing Advanced Solid Tumors MGH Open D
NCT01391143 Safety Study of MGA271 in Refractory Cancer Safety Study of MGA271 in Refractory Cancer MGH Open D
NCT02576431 Study of LOXO-101 in Subjects With NTRK Fusion Positive Solid Tumors (NAVIGATE) Study of LOXO-101 in Subjects With NTRK Fusion Positive Solid Tumors (NAVIGATE) MGH Open D
Trial Status: Showing Results: 1-10 of 14 Per Page:
12Next »
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