NF2, all inactivating mutations

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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 http://targetedcancercare.massgeneral.org/My-Trial-Guide/Genes/NF2.aspx Gene Accordion Expanded

Expand Collapse all inactivating mutations  in NF2 http://targetedcancercare.massgeneral.org/My-Trial-Guide/Genes/NF2/all-inactivating-mutations.aspx Mutation Accordion Expanded