Brain Tumors, EGFR, Gene Amplification

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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 EGFR  - General Description
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The EGFR gene encodes for a cell-surface protein known as the epidermal growth factor receptor, which is found in many normal epithelial tissues such as the skin and hair follicles. When epidermal growth factor ligand bind to EGFR, they activate several different cell signaling pathways that control various cell functions, including cell growth and proliferation.

Mutations in EGFR can lead to unregulated activation of the protein. These types of activating mutations are often found in NSCLC (non-small cell lung cancer), glioblastoma and head and neck squamous cell carcinoma. Sometimes, excess EGFR protein is produced due to the presence of too many copies of the EGFR gene, leading to excessive cell division and growth in the presence of epidermal growth factor. Among the human cancers in which EGFR overabundance is present are cancers of the head and neck (squamous cell), colon, rectum, lung (NSCLC), central nervous system (glioblastoma), pancreas and breast (HER2-positive metastatic). Blocking EGFR in tumors may keep cancer cells from growing. The FDA has approved several therapies that target EGFR in one or more cancers. Testing for genetic alterations of EGFR is available at the MGH genetics lab. Treatment for EGFR-mutant tumors, along with clinical trials testing new drugs for the treatment of EGFR-mutant tumors are available at the MGH Cancer Center.

Tumor mutation profiling performed clinically at the MGH Cancer Center has indicated that EGFR mutations occur primarily in lung cancer (~15%), but also in a minor subset of gastric (2%), brain (1%) and pancreatic (1%) cancers.

Source: Genetics Home Reference
The EGFR gene encodes for a cell-surface protein known as the epidermal growth factor receptor, which is found in many normal epithelial tissues such as the skin and hair follicles. When epidermal growth factor ligand bind to EGFR, they activate several different cell signaling pathways that control various cell functions, including cell growth and proliferation.

Mutations in EGFR can lead to unregulated activation of the protein. These types of activating mutations are often found in NSCLC (non-small cell lung cancer), glioblastoma and head and neck squamous cell carcinoma. Sometimes, excess EGFR protein is produced due to the presence of too many copies of the EGFR gene, leading to excessive cell division and growth in the presence of epidermal growth factor. Among the human cancers in which EGFR overabundance is present are cancers of the head and neck (squamous cell), colon, rectum, lung (NSCLC), central nervous system (glioblastoma), pancreas and breast (HER2-positive metastatic). Blocking EGFR in tumors may keep cancer cells from growing. The FDA has approved several therapies that target EGFR in one or more cancers. Testing for genetic alterations of EGFR is available at the MGH genetics lab. Treatment for EGFR-mutant tumors, along with clinical trials testing new drugs for the treatment of EGFR-mutant tumors are available at the MGH Cancer Center.

Tumor mutation profiling performed clinically at the MGH Cancer Center has indicated that EGFR mutations occur primarily in lung cancer (~15%), but also in a minor subset of gastric (2%), brain (1%) and pancreatic (1%) cancers.

Source: Genetics Home Reference
PubMed ID's
15864276, 15118073, 15118125, 15329413, 18772890, 15837736, 16720329, 21057220
Expand Collapse Gene Amplification  in EGFR
Gene amplification is a genetic alteration that occurs when a region of DNA that contains a gene is duplicated-sometimes multiple times. Amplification of the EGFR gene results in more EGF receptors being produced, or "EGFR overexpression". The cells with this genetic alteration have a much higher level of EGFR, which disrupts normal regulation of the EGFR. This results in a stronger signal to grow and proliferate, contributing to the development of cancer.
Gene amplification is a genetic alteration that occurs when a region of DNA that contains a gene is duplicated-sometimes multiple times. Amplification of the EGFR gene results in more EGF receptors being produced, or "EGFR overexpression". The cells with this genetic alteration have a much higher level of EGFR, which disrupts normal regulation of the EGFR. This results in a stronger signal to grow and proliferate, contributing to the development of cancer.

Amplification of the EGFR gene, which leads to increased activity of the EGFR pathway, is found in 40-50% of glioblastomas. Additionally, activating mutations in the extracellular domain of EGFR are frequently observed in glioblastoma, including EGFRvIII mutation (25-33%) and point mutations (10-15%). Approximately one half of the EGFR gene amplified cases carry the EGFRvIII mutation.

In contrast to what has been demonstrated in lung cancer, multiple clinical trials conducted in brain cancer have generally reported that current EGFR small molecule inhibitors (primarily erlotinib or gefitinib) are not effective in the treatment of high-grade gliomas. Furthermore, there has been no clear association between the presence of EGFR amplification or EGFR mutation (EGFRvIII) and response to these EGFR-targeted agents. Recent laboratory studies have indicated that drug combinations, which target the inhibition of EGFR together with additional receptor tyrosine kinases or the PI3-kinase pathway, may be a more effective strategy.

Amplification of the EGFR gene, which leads to increased activity of the EGFR pathway, is found in 40-50% of glioblastomas. Additionally, activating mutations in the extracellular domain of EGFR are frequently observed in glioblastoma, including EGFRvIII mutation (25-33%) and point mutations (10-15%). Approximately one half of the EGFR gene amplified cases carry the EGFRvIII mutation.

In contrast to what has been demonstrated in lung cancer, multiple clinical trials conducted in brain cancer have generally reported that current EGFR small molecule inhibitors (primarily erlotinib or gefitinib) are not effective in the treatment of high-grade gliomas. Furthermore, there has been no clear association between the presence of EGFR amplification or EGFR mutation (EGFRvIII) and response to these EGFR-targeted agents. Recent laboratory studies have indicated that drug combinations, which target the inhibition of EGFR together with additional receptor tyrosine kinases or the PI3-kinase pathway, may be a more effective strategy.

PubMed ID's
22701710, 18281526, 14583498, 14638850, 17353924, 16282176, 16278407, 19204207, 22323597, 21471286, 22268382, 15956649, 17804702, 16912159
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Your Matched Clinical Trials

Trial Matches: (D) - Disease, (G) - Gene, (M) - Mutation
Trial Status: Showing Results: 1-10 of 39 Per Page:
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Protocol # Title Location Status Match
NCT01986348 A Phase 2 Study Evaluating the Efficacy and Safety of Selinexor (KPT-330) in Patients With Recurrent Gliomas A Phase 2 Study Evaluating the Efficacy and Safety of Selinexor (KPT-330) in Patients With Recurrent Gliomas MGH Open D
NCT02431572 A Pilot Study to Evaluate PBR PET in Brain Tumor Patients Treated With Chemoradiation or Immunotherapy A Pilot Study to Evaluate PBR PET in Brain Tumor Patients Treated With Chemoradiation or Immunotherapy MGH Open D
NCT03150862 A Study Assessing BGB-290 With Radiation and/or Temozolomide (TMZ) in Subjects With Newly Diagnosed or Recurrent Glioblastoma A Study Assessing BGB-290 With Radiation and/or Temozolomide (TMZ) in Subjects With Newly Diagnosed or Recurrent Glioblastoma MGH Open D
NCT02981940 A Study of Abemaciclib in Recurrent Glioblastoma A Study of Abemaciclib in Recurrent Glioblastoma MGH Open D
NCT03013218 A Study of ALX148 in Patients With Advanced Solid Tumors and Lymphoma A Study of ALX148 in Patients With Advanced Solid Tumors and Lymphoma 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
NCT02428712 A Study of PLX8394 as a Single Agent in Patients With Advanced Unresectable Solid Tumors A Study of PLX8394 as a Single Agent in Patients With Advanced Unresectable Solid Tumors MGH Open D
NCT02693990 A Trial of Increased Dose Intensity Modulated Proton Therapy (IMPT) for High-Grade Meningiomas A Trial of Increased Dose Intensity Modulated Proton Therapy (IMPT) for High-Grade Meningiomas MGH Open D
NCT02748135 A Two-Part Study of TB-403 in Pediatric Subjects With Relapsed or Refractory Medulloblastoma A Two-Part Study of TB-403 in Pediatric Subjects With Relapsed or Refractory Medulloblastoma MGH Open D
NCT02617589 An Investigational Immuno-therapy Study of Nivolumab Compared to Temozolomide, Each Given With Radiation Therapy, for Newly-diagnosed Patients With Glioblastoma (GBM, a Malignant Brain Cancer) An Investigational Immuno-therapy Study of Nivolumab Compared to Temozolomide, Each Given With Radiation Therapy, for Newly-diagnosed Patients With Glioblastoma (GBM, a Malignant Brain Cancer) MGH Open D
Trial Status: Showing Results: 1-10 of 39 Per Page:
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