Brain Tumors, TP53

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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 TP53  - General Description
CLICK IMAGE FOR MORE INFORMATION
The p53 (TP53) gene produces a protein, P53 which has many complex functions within the cell. It has been called the “guardian of the genome” for reasons that have to do with these complex functions. Normal, non-cancerous cells have tightly regulated pathways that control cell growth, mediating cessation of growth or even cell death when circumstances warrant it. P53 is at the center of these pathways, acting as a “tumor suppressor” in responding to circumstances in the cell that require a cessation of growth. Perhaps for this reason, P53 is one of the most commonly mutated genes across all cancer types.

P53 itself regulates the expression of several genes that are involved in growth arrest or “cell cycle arrest”. Growth arrest is important for stopping the cell from normal growth and cell division so that if, for instance, there has been damage to the DNA from UV irradiation or some other insult causing DNA damage, the cessation of the cell cycle allows DNA repair to take place before the cell resumes growth. If the damage to the DNA is too extensive to repair, or if other factors such as oncogenic stress impact the cell, P53 then has roles in other processes that are part of the cell’s repertoire of responses. These include processes such as apoptosis (programmed cell death), senescence (irreversible cell cycle arrest), autophagy (regulated destruction of selected proteins within the cell, leading to cell death), and some important metabolic changes in the cell (see graphic above, adapted with permission).

P53 is itself acted upon by proteins in the cell that detect DNA damage or oncogenic stress (see graphic depicting P53 at the center of a number of cellular responses). In the case of DNA damage to the cell, P53 is acted upon by a protein called ATM and another designated CHK2 (see glossary for more information). These proteins activate P53 to regulate the changes that will cause growth arrest. Interestingly, these two genes themselves are found to be mutated and have altered function in certain cancers. The fact that both P53 and the genes that trigger P53’s response and initiation of growth arrest are mutated in some cancers highlights the importance of P53 to normal cell growth. P53 is found to be mutated in over half of cancers studied, including ovarian cancer, colon and esophageal cancer, and many other types of cancer. Because p53 plays so many complex roles in the cell, we do not depict it in a simple graphic as we have with other proteins on this web site in which genetic alterations have been found in specific tumors that lead to dysregulation of these proteins. Rather, P53 as a negative regulator of cell growth under important circumstances plays this role at the center of a complex network of pathways within the cell. Many of the proteins involved in the pathways that regulate P53 and its responses are also found to be genetically altered in some cancers.

As we have seen, the P53 protein has many functions in the cell, and because of these many roles, its location in the nucleus or cytoplasm varies, depending on the function and when it exerts its effect during the cell cycle. One important protein that regulates P53 is called HDM2/MDM2, depicted in the graphic above. The HDM2/MDM2 protein contains a p53 binding domain, and once bound to p53, it inhibits the activation of the P53 protein, and thereby prevents P53 from regulating growth arrest, even when there is damage to the DNA. Some cancers have been found to overexpress HDM2/MDM2, meaning there is an excess of the protein which binds to P53, preventing it from exerting its important role in regulating growth arrest. Cell division that occurs despite damage to the DNA can lead to cancer. Interestingly, those cancers that have been found to over-express HDM2/MDM2 typically are not found to have p53 mutations. This provides scientists with evidence that by whatever means, either through increasing the amount of the P53 inhibitor HDM2/MDM2, or, through mutations in P53 that prevent the normal activities of the protein, the normal function of P53 is important in preventing cancer. MDM2 was named after its discovery in studies on laboratory mice. The human version of the gene is designated HumanDM2, or HDM2. Genetic alterations leading to over-expression of MDM2 are observed most commonly in sarcomas, but have also been observed in endometrial cancer, colon cancer, and stomach cancer.

Source: Molecular Genetics of Cancer, Second Edition
Chapter No. 2, Section No. 12
Leif W. Ellisen, MD, PhD
The p53 (TP53) gene produces a protein, P53 which has many complex functions within the cell. It has been called the “guardian of the genome” for reasons that have to do with these complex functions. Normal, non-cancerous cells have tightly regulated pathways that control cell growth, mediating cessation of growth or even cell death when circumstances warrant it. P53 is at the center of these pathways, acting as a “tumor suppressor” in responding to circumstances in the cell that require a cessation of growth. Perhaps for this reason, P53 is one of the most commonly mutated genes across all cancer types.

P53 itself regulates the expression of several genes that are involved in growth arrest or “cell cycle arrest”. Growth arrest is important for stopping the cell from normal growth and cell division so that if, for instance, there has been damage to the DNA from UV irradiation or some other insult causing DNA damage, the cessation of the cell cycle allows DNA repair to take place before the cell resumes growth. If the damage to the DNA is too extensive to repair, or if other factors such as oncogenic stress impact the cell, P53 then has roles in other processes that are part of the cell’s repertoire of responses. These include processes such as apoptosis (programmed cell death), senescence (irreversible cell cycle arrest), autophagy (regulated destruction of selected proteins within the cell, leading to cell death), and some important metabolic changes in the cell (see graphic above, adapted with permission).

P53 is itself acted upon by proteins in the cell that detect DNA damage or oncogenic stress (see graphic depicting P53 at the center of a number of cellular responses). In the case of DNA damage to the cell, P53 is acted upon by a protein called ATM and another designated CHK2 (see glossary for more information). These proteins activate P53 to regulate the changes that will cause growth arrest. Interestingly, these two genes themselves are found to be mutated and have altered function in certain cancers. The fact that both P53 and the genes that trigger P53’s response and initiation of growth arrest are mutated in some cancers highlights the importance of P53 to normal cell growth. P53 is found to be mutated in over half of cancers studied, including ovarian cancer, colon and esophageal cancer, and many other types of cancer. Because p53 plays so many complex roles in the cell, we do not depict it in a simple graphic as we have with other proteins on this web site in which genetic alterations have been found in specific tumors that lead to dysregulation of these proteins. Rather, P53 as a negative regulator of cell growth under important circumstances plays this role at the center of a complex network of pathways within the cell. Many of the proteins involved in the pathways that regulate P53 and its responses are also found to be genetically altered in some cancers.

As we have seen, the P53 protein has many functions in the cell, and because of these many roles, its location in the nucleus or cytoplasm varies, depending on the function and when it exerts its effect during the cell cycle. One important protein that regulates P53 is called HDM2/MDM2, depicted in the graphic above. The HDM2/MDM2 protein contains a p53 binding domain, and once bound to p53, it inhibits the activation of the P53 protein, and thereby prevents P53 from regulating growth arrest, even when there is damage to the DNA. Some cancers have been found to overexpress HDM2/MDM2, meaning there is an excess of the protein which binds to P53, preventing it from exerting its important role in regulating growth arrest. Cell division that occurs despite damage to the DNA can lead to cancer. Interestingly, those cancers that have been found to over-express HDM2/MDM2 typically are not found to have p53 mutations. This provides scientists with evidence that by whatever means, either through increasing the amount of the P53 inhibitor HDM2/MDM2, or, through mutations in P53 that prevent the normal activities of the protein, the normal function of P53 is important in preventing cancer. MDM2 was named after its discovery in studies on laboratory mice. The human version of the gene is designated HumanDM2, or HDM2. Genetic alterations leading to over-expression of MDM2 are observed most commonly in sarcomas, but have also been observed in endometrial cancer, colon cancer, and stomach cancer.

Source: Molecular Genetics of Cancer, Second Edition
Chapter No. 2, Section No. 12
Leif W. Ellisen, MD, PhD
Expand Collapse TP53  in Brain Tumors
Currently there is no known direct therapeutic role of TP53 mutations in gliomas.

The is contradictory published data regarding the prognostic implications of p53 mutations in gliomas (Ohgaki and Kleihues, 2005). If there is an effect, it is small.

Currently there is no known direct therapeutic role of TP53 mutations in gliomas.

The is contradictory published data regarding the prognostic implications of p53 mutations in gliomas (Ohgaki and Kleihues, 2005). If there is an effect, it is small.

PubMed ID's
15977639
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 Results: 1-10 of 12 Per Page:
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NCT02481154 Study of Orally Administered AG-881 in Patients With Advanced Solid Tumors, Including Gliomas, With an IDH1 and/or IDH2 Mutation Study of Orally Administered AG-881 in Patients With Advanced Solid Tumors, Including Gliomas, With an IDH1 and/or IDH2 Mutation MGH Open D
Trial Status: Showing Results: 1-10 of 12 Per Page:
12Next »
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