Gastric/Esophageal, APC, mutation (insertion, deletion, mutation)

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Expand Collapse Gastric/Esophageal  - General Description Cancers of the stomach and esophagus, can also collectively be referred to as gastroesophageal or esophagogastric cancer. Gastric cancer incidence varies throughout the world, with a higher frequency in some countries-perhaps due to different diets or other factors. Esophageal cancers are more common in men than in women. Both alcohol use and tobacco use are associated with a higher risk of developing gastric or esophageal cancer. According to the National Cancer Institute (NCI) data, 16,940 men and 15,690 women were projected to be diagnosed with gastric cancer in the United States in 2017.

Most cancers involving the esophagus or stomach are either squamous cell cancer (SCC) or adenocarcinoma. Gastric and esophageal cancers tend to develop slowly over many years in the inner mucosal layer of the stomach or esophagus. These early changes rarely cause symptoms, and therefore frequently go undetected. As esophageal and gastric cancers become more advanced, symptoms become more apparent. Once symptoms bring a patient to a doctor for medical attention, the diagnosis can be made. Thorough diagnostics are available at the MGH, initially involving an endoscopic biopsy, which is used to definitively diagnose the cancer by experienced Pathologists. Subsequent to a confirmed diagnosis, it is important to stage the cancer which includes in-depth pathology analysis, as well as a radiographic imaging procedure such as CT or PET scan. Often lymph nodes near the cancer are analysed to insure the cancer has not spread.

There has been a growing interest in the molecular features of esophageal and gastric cancers, as genetic alterations in these cancers have been identified in patients. Some genes that have been found to be involved in these two cancer types are mutations or amplification of the genes that encode HER2, MET or EGFR. Other genetic alterations have also been identified. Testing for these genetic alterations is performed in the genetics lab of the MGH, enabling physicians to utilize targeted therapies tailored for individual tumors. Treatment options for esophageal and gastric cancers are available at the MGH Cancer Center, as well as Clinical Trials testing new treatments for patients with this diagnosis.

Source: National Cancer Institute, 2018
Cancers of the stomach and esophagus, can also collectively be referred to as gastroesophageal or esophagogastric cancer. Gastric cancer incidence varies throughout the world, with a higher frequency in some countries-perhaps due to different diets or other factors. Esophageal cancers are more common in men than in women. Both alcohol use and tobacco use are associated with a higher risk of developing gastric or esophageal cancer. According to the National Cancer Institute (NCI) data, 16,940 men and 15,690 women were projected to be diagnosed with gastric cancer in the United States in 2017.

Most cancers involving the esophagus or stomach are either squamous cell cancer (SCC) or adenocarcinoma. Gastric and esophageal cancers tend to develop slowly over many years in the inner mucosal layer of the stomach or esophagus. These early changes rarely cause symptoms, and therefore frequently go undetected. As esophageal and gastric cancers become more advanced, symptoms become more apparent. Once symptoms bring a patient to a doctor for medical attention, the diagnosis can be made. Thorough diagnostics are available at the MGH, initially involving an endoscopic biopsy, which is used to definitively diagnose the cancer by experienced Pathologists. Subsequent to a confirmed diagnosis, it is important to stage the cancer which includes in-depth pathology analysis, as well as a radiographic imaging procedure such as CT or PET scan. Often lymph nodes near the cancer are analysed to insure the cancer has not spread.

There has been a growing interest in the molecular features of esophageal and gastric cancers, as genetic alterations in these cancers have been identified in patients. Some genes that have been found to be involved in these two cancer types are mutations or amplification of the genes that encode HER2, MET or EGFR. Other genetic alterations have also been identified. Testing for these genetic alterations is performed in the genetics lab of the MGH, enabling physicians to utilize targeted therapies tailored for individual tumors. Treatment options for esophageal and gastric cancers are available at the MGH Cancer Center, as well as Clinical Trials testing new treatments for patients with this diagnosis.

Source: National Cancer Institute, 2018
Cancers of the stomach and esophagus, can also collectively be referred to as gastroesophageal or esophagogastric cancer. Gastric cancer incidence varies throughout the world, with a higher frequency in some countries-perhaps due to different diets or other factors. Esophageal cancers are more common in men than in women. Both alcohol use and tobacco use are associated with a higher risk of developing gastric or esophageal cancer. According to the National Cancer Institute (NCI) data, 16,940 men and 15,690 women were projected to be diagnosed with gastric cancer in the United States in 2017.

Most cancers involving the esophagus or stomach are either squamous cell cancer (SCC) or adenocarcinoma. Gastric and esophageal cancers tend to develop slowly over many years in the inner mucosal layer of the stomach or esophagus. These early changes rarely cause symptoms, and therefore frequently go undetected. As esophageal and gastric cancers become more advanced, symptoms become more apparent. Once symptoms bring a patient to a doctor for medical attention, the diagnosis can be made. Thorough diagnostics are available at the MGH, initially involving an endoscopic biopsy, which is used to definitively diagnose the cancer by experienced Pathologists. Subsequent to a confirmed diagnosis, it is important to stage the cancer which includes in-depth pathology analysis, as well as a radiographic imaging procedure such as CT or PET scan. Often lymph nodes near the cancer are analysed to insure the cancer has not spread.

There has been a growing interest in the molecular features of esophageal and gastric cancers, as genetic alterations in these cancers have been identified in patients. Some genes that have been found to be involved in these two cancer types are mutations or amplification of the genes that encode HER2, MET or EGFR. Other genetic alterations have also been identified. Testing for these genetic alterations is performed in the genetics lab of the MGH, enabling physicians to utilize targeted therapies tailored for individual tumors. Treatment options for esophageal and gastric cancers are available at the MGH Cancer Center, as well as Clinical Trials testing new treatments for patients with this diagnosis.

Source: National Cancer Institute, 2018
Cancers of the stomach and esophagus, can also collectively be referred to as gastroesophageal or esophagogastric cancer. Gastric cancer incidence varies throughout the world, with a higher frequency in some countries-perhaps due to different diets or other factors. Esophageal cancers are more common in men than in women. Both alcohol use and tobacco use are associated with a higher risk of developing gastric or esophageal cancer. According to the National Cancer Institute (NCI) data, 16,940 men and 15,690 women were projected to be diagnosed with gastric cancer in the United States in 2017.

Most cancers involving the esophagus or stomach are either squamous cell cancer (SCC) or adenocarcinoma. Gastric and esophageal cancers tend to develop slowly over many years in the inner mucosal layer of the stomach or esophagus. These early changes rarely cause symptoms, and therefore frequently go undetected. As esophageal and gastric cancers become more advanced, symptoms become more apparent. Once symptoms bring a patient to a doctor for medical attention, the diagnosis can be made. Thorough diagnostics are available at the MGH, initially involving an endoscopic biopsy, which is used to definitively diagnose the cancer by experienced Pathologists. Subsequent to a confirmed diagnosis, it is important to stage the cancer which includes in-depth pathology analysis, as well as a radiographic imaging procedure such as CT or PET scan. Often lymph nodes near the cancer are analysed to insure the cancer has not spread.

There has been a growing interest in the molecular features of esophageal and gastric cancers, as genetic alterations in these cancers have been identified in patients. Some genes that have been found to be involved in these two cancer types are mutations or amplification of the genes that encode HER2, MET or EGFR. Other genetic alterations have also been identified. Testing for these genetic alterations is performed in the genetics lab of the MGH, enabling physicians to utilize targeted therapies tailored for individual tumors. Treatment options for esophageal and gastric cancers are available at the MGH Cancer Center, as well as Clinical Trials testing new treatments for patients with this diagnosis.

Source: National Cancer Institute, 2018
Expand Collapse APC  - General Description
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Adenomatous Polyposis Coli (APC) is a regulator of several fundamental cellular processes, including cell division, cell attachment, cell migration, cell polarization, and chromosome segregation during division. In these complex functions, APC activity is essential for the prevention of cancer (in other words, APC acts as a tumor suppressor). APC is involved in these cellular functions through interactions with other cellular proteins. One of the most recognized functions of APC is in regulating levels of beta-catenin, which is part of the WNT signal pathway in cells.

The WNT signal pathway is important in a variety of cellular processes. In the left hand cell in the graphic above, one can see that when there is no WNT ligand to bind to the extracellular WNT receptor, APC exists in a complex with other proteins. The complex is known as the “destruction complex”, and acts to destroy beta-catenin in the cell cytoplasm. This keeps levels of beta-catenin in the cell very low. Beta-catenin also binds to E-cadherin at the cell membrane, and is involved in cell to cell contacts (see graphic).

When WNT ligand binds to the extracellular WNT receptor, as is depicted in the right hand cell in the graphic above, it activates the receptor to send a signal that causes the dissociation of the destruction complex including APC. Without the destruction complex, beta-catenin builds up in the cytoplasm of the cells. In the cytoplasm, beta-catenin binds to T-cell factor (TCF), and together they translocate into the nucleus. They then bind to DNA and activate the transcription of genes that promote cell growth, such as c-Myc and cyclin D1. In the presence of WNT ligand binding, normal cells proliferate and divide.

In some cancers, APC is genetically altered, either through mutation or actual loss of the gene. Mutations in APC have been found in most colon cancers, whether familial (inherited genetic alterations) or spontaneous (somatic gene mutation). Mutations in APC have also been found in other cancers, including in adenocarcinoma of the lung. When APC is missing or mutated it cannot function in the destruction complex, and beta-catenin builds up in the cytoplasm even in the absence of WNT signaling. This unregulated high level of beta-catenin binds to TCF, moves into the nucleus of cancer cells, and binds to DNA to stimulate transcription of c-Myc and cyclin D1, causing cells to grow and divide.

Another way that APC function can be disrupted is through changes in E-cadherin, a protein that binds to beta-catenin, and mediates cell to cell contact (see graphic above). In many cancers, E-cadherin expression is lost, and without E-cadherin interacting with beta-catenin, cell to cell contact becomes dysregulated. Other genetic changes in E-cadherin can be inherited. The gene that encodes E-cadherin is called CDH1. Inherited germline mutations in CDH1 result in an E-cadherin protein that does not function normally, and these inherited mutations in CDH1/E-cadherin have been found to be associated with Hereditary Diffuse Gastric cancer/Lobular Breast Cancer Syndrome. The fact that so many genetic alterations in the pathways associated with APC highlight the importance of the APC tumor suppressor in normally preventing cancer.


Sources:
Graphic adapted from slideshareecdn.com 02-cat-neoplasia-5081/95/02-cat-neoplasia-14-728.jpg?cb=124463107
Valeria Bugos, Camila Guezada, Nicolas Briceno
Text sources PMID#17881494 Adenomatous polyposis coli (APC): a multi-functional tumor suppressor gene

Adenomatous Polyposis Coli (APC) is a regulator of several fundamental cellular processes, including cell division, cell attachment, cell migration, cell polarization, and chromosome segregation during division. In these complex functions, APC activity is essential for the prevention of cancer (in other words, APC acts as a tumor suppressor). APC is involved in these cellular functions through interactions with other cellular proteins. One of the most recognized functions of APC is in regulating levels of beta-catenin, which is part of the WNT signal pathway in cells.

The WNT signal pathway is important in a variety of cellular processes. In the left hand cell in the graphic above, one can see that when there is no WNT ligand to bind to the extracellular WNT receptor, APC exists in a complex with other proteins. The complex is known as the “destruction complex”, and acts to destroy beta-catenin in the cell cytoplasm. This keeps levels of beta-catenin in the cell very low. Beta-catenin also binds to E-cadherin at the cell membrane, and is involved in cell to cell contacts (see graphic).

When WNT ligand binds to the extracellular WNT receptor, as is depicted in the right hand cell in the graphic above, it activates the receptor to send a signal that causes the dissociation of the destruction complex including APC. Without the destruction complex, beta-catenin builds up in the cytoplasm of the cells. In the cytoplasm, beta-catenin binds to T-cell factor (TCF), and together they translocate into the nucleus. They then bind to DNA and activate the transcription of genes that promote cell growth, such as c-Myc and cyclin D1. In the presence of WNT ligand binding, normal cells proliferate and divide.

In some cancers, APC is genetically altered, either through mutation or actual loss of the gene. Mutations in APC have been found in most colon cancers, whether familial (inherited genetic alterations) or spontaneous (somatic gene mutation). Mutations in APC have also been found in other cancers, including in adenocarcinoma of the lung. When APC is missing or mutated it cannot function in the destruction complex, and beta-catenin builds up in the cytoplasm even in the absence of WNT signaling. This unregulated high level of beta-catenin binds to TCF, moves into the nucleus of cancer cells, and binds to DNA to stimulate transcription of c-Myc and cyclin D1, causing cells to grow and divide.

Another way that APC function can be disrupted is through changes in E-cadherin, a protein that binds to beta-catenin, and mediates cell to cell contact (see graphic above). In many cancers, E-cadherin expression is lost, and without E-cadherin interacting with beta-catenin, cell to cell contact becomes dysregulated. Other genetic changes in E-cadherin can be inherited. The gene that encodes E-cadherin is called CDH1. Inherited germline mutations in CDH1 result in an E-cadherin protein that does not function normally, and these inherited mutations in CDH1/E-cadherin have been found to be associated with Hereditary Diffuse Gastric cancer/Lobular Breast Cancer Syndrome. The fact that so many genetic alterations in the pathways associated with APC highlight the importance of the APC tumor suppressor in normally preventing cancer.


Sources:
Graphic adapted from slideshareecdn.com 02-cat-neoplasia-5081/95/02-cat-neoplasia-14-728.jpg?cb=124463107
Valeria Bugos, Camila Guezada, Nicolas Briceno
Text sources PMID#17881494 Adenomatous polyposis coli (APC): a multi-functional tumor suppressor gene

PubMed ID's
1788494,
Expand Collapse mutation (insertion, deletion, mutation)  in APC
Both germline (inherited) as well as somatic (acquired after birth) mutations in the APC gene have been found in tumors, especially colorectal cancers. These genetic mutations can include changes in nucleotides in a region of the APC gene in exon 15 called the Mutation Cluster Region (MCR), or in other regions of the APC gene. Other muatational changes associated with colorectal cancers involve insertions of a number of nucleotides in the genetic code, or, alternatively, a deletion or section where there are missing nucleotides. Virtually all of the mutations found in APC result in a truncated protein, an abnormal protein missing important functional regions of APC.
Both germline (inherited) as well as somatic (acquired after birth) mutations in the APC gene have been found in tumors, especially colorectal cancers. These genetic mutations can include changes in nucleotides in a region of the APC gene in exon 15 called the Mutation Cluster Region (MCR), or in other regions of the APC gene. Other muatational changes associated with colorectal cancers involve insertions of a number of nucleotides in the genetic code, or, alternatively, a deletion or section where there are missing nucleotides. Virtually all of the mutations found in APC result in a truncated protein, an abnormal protein missing important functional regions of APC.

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Your Matched Clinical Trials

Trial Matches: (D) - Disease, (G) - Gene, (M) - Mutation
Trial Status: Showing all 4 results Per Page:
Protocol # Title Location Status Match
NCT02099058 A Study Evaluating the Safety, Pharmacokinetics (PK), and Preliminary Efficacy of ABBV-399 in Subjects With Advanced Solid Tumors A Study Evaluating the Safety, Pharmacokinetics (PK), and Preliminary Efficacy of ABBV-399 in Subjects With Advanced Solid Tumors MGH Open D
NCT01325441 A Study of BBI608 Administered With Paclitaxel in Adult Patients With Advanced Malignancies A Study of BBI608 Administered With Paclitaxel in Adult Patients With Advanced Malignancies MGH Open D
NCT01953926 Neratinib HER Mutation Basket Study (SUMMIT) Neratinib HER Mutation Basket Study (SUMMIT) MGH Open D
NCT02079740 Trametinib and Navitoclax in Treating Patients With Advanced or Metastatic Solid Tumors Trametinib and Navitoclax in Treating Patients With Advanced or Metastatic Solid Tumors 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 4 results Per Page:

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