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Expand Collapse Colorectal Cancer  - General Description Colorectal Cancer (CRC) is cancer that initiates in the colon or rectum-the lower part of the digestive system in the body. During digestion, food moves through the stomach and small intestine into the colon. The colon absorbs water and nutrients from food, and stores waste matter (stool) that moves from the colon through the rectum before leaving the body.

Most CRC's and rectal cancers are adenocarcinomas, meaning that they originate in cells that make and release mucus and other fluids. CRC often begins as a growth called a polyp, which may form on the inner wall of the colon or rectum. Over time, some polyps become cancerous. This highlights the importance of colonoscopy screening to find and remove polyps before they become cancerous.

CRC is the fourth most common type of cancer diagnosed in the U.S. Deaths from CRC have decreased with the use of colonoscopies and fecal occult blood tests, which check for blood in the stool. Disparities in survival have been observed between African American and other populations. This may be due to factors such as access to colonoscopy screening, or to other factors not yet identified.

Because of its prevalence, scientists have studied CRC extensively, even creating models of how cancer develops using CRC as an example. There are also families with a very high incidence of CRC occurrence. When these families were studied, certain conditions that create instability in the whole genome were identified that predispose people to CRC. These include what is called the chromosomal instability pathway (CIN) as well as microsatellite instability pathway (MSI). Both of these are recognized pathways in the development of CRC. These types of genetic instability lead to activation of proto-oncogenes such as KRAS, and the inactivation of tumor suppressors mentioned below.

Other genetic alterations in how the DNA in cells is organized have been found to contribute to CRC in families and individuals. These are called epigenetic changes. Normal DNA has methyl groups added in specific regions that regulate gene expression. When the genes that suppress growth-called tumor suppressors-are methylated in abnormal patterns, this prevents the production of tumor suppressor proteins that are important in controlling or stopping cell growth. When these are missing, unregulated growth occurs, contributing to the development of cancer. Some tumor suppressor proteins that are frequently inactivated in CRC are APC, TP53, and loss of one arm of chromosome 18 that contains a tumor suppressor.

The study of families with a high prevalence of CRC have lead scientists to discover genetic changes that contribute to the development of CRC in sporadic cases occurring in patients. Mutations in the genes encoding the following proteins have now been associated with subsets of CRC; AKT, APC, beta-catenin, BRAF, EGFR, ERBB2, ERBB3, IDH2, KRAS, NRAS, PIk3CA, PTEN, TP53,TRK 1, 2 and 3, and others still being identified.

Finally, distinct familial syndromes of CRC such as Lynch syndrome have been studied, and in these patients, the normal proof-reading of DNA during cell replication is found to be deficient. While DNA polymerase enzyme is replicating DNA before cells divide (with both daughter cells having a full complement of DNA), it occasionally makes errors. In a process of proof-reading behind this enzyme, several proteins form a complex to find and repair these mistakes. The process of proof-reading and restoring the DNA to the correct sequence is called mismatch repair (MMR). In Lynch syndrome, one or more of the proteins involved in MMR is mutated, and the mistakes in the DNA do not get corrected. The accumulation of these mistakes or mutations leads to cancer. Mutations in MMR proteins are not only found in familial cases of CRC, but also in patients with sporadic CRC. DNA repair machinery in the cell is important in keeping the genome stable and accurate. Defects in MMR also contribute to microsatellite instability (MIS), described above.

Testing for the mutations and genomic conditions that contribute to the development or progression of CRC are available at MGH in the sophisticated CLIA certified genomic testing lab, and in other large Centers and some private testing companies used by physicians. Validated treatments as well as clinical trials investigating improved targeted and immunologic therapies are available to patients at MGH.

NIH/NCI Cancer Website www.cancer.gov 2017
Genetic Alterations in CRC; Gastrointestinal Cancer Research; Amaghany T, et al.
Colorectal Cancer (CRC) is cancer that initiates in the colon or rectum-the lower part of the digestive system in the body. During digestion, food moves through the stomach and small intestine into the colon. The colon absorbs water and nutrients from food, and stores waste matter (stool) that moves from the colon through the rectum before leaving the body.

Most CRC's and rectal cancers are adenocarcinomas, meaning that they originate in cells that make and release mucus and other fluids. CRC often begins as a growth called a polyp, which may form on the inner wall of the colon or rectum. Over time, some polyps become cancerous. This highlights the importance of colonoscopy screening to find and remove polyps before they become cancerous.

CRC is the fourth most common type of cancer diagnosed in the U.S. Deaths from CRC have decreased with the use of colonoscopies and fecal occult blood tests, which check for blood in the stool. Disparities in survival have been observed between African American and other populations. This may be due to factors such as access to colonoscopy screening, or to other factors not yet identified.

Because of its prevalence, scientists have studied CRC extensively, even creating models of how cancer develops using CRC as an example. There are also families with a very high incidence of CRC occurrence. When these families were studied, certain conditions that create instability in the whole genome were identified that predispose people to CRC. These include what is called the chromosomal instability pathway (CIN) as well as microsatellite instability pathway (MSI). Both of these are recognized pathways in the development of CRC. These types of genetic instability lead to activation of proto-oncogenes such as KRAS, and the inactivation of tumor suppressors mentioned below.

Other genetic alterations in how the DNA in cells is organized have been found to contribute to CRC in families and individuals. These are called epigenetic changes. Normal DNA has methyl groups added in specific regions that regulate gene expression. When the genes that suppress growth-called tumor suppressors-are methylated in abnormal patterns, this prevents the production of tumor suppressor proteins that are important in controlling or stopping cell growth. When these are missing, unregulated growth occurs, contributing to the development of cancer. Some tumor suppressor proteins that are frequently inactivated in CRC are APC, TP53, and loss of one arm of chromosome 18 that contains a tumor suppressor.

The study of families with a high prevalence of CRC have lead scientists to discover genetic changes that contribute to the development of CRC in sporadic cases occurring in patients. Mutations in the genes encoding the following proteins have now been associated with subsets of CRC; AKT, APC, beta-catenin, BRAF, EGFR, ERBB2, ERBB3, IDH2, KRAS, NRAS, PIk3CA, PTEN, TP53,TRK 1, 2 and 3, and others still being identified.

Finally, distinct familial syndromes of CRC such as Lynch syndrome have been studied, and in these patients, the normal proof-reading of DNA during cell replication is found to be deficient. While DNA polymerase enzyme is replicating DNA before cells divide (with both daughter cells having a full complement of DNA), it occasionally makes errors. In a process of proof-reading behind this enzyme, several proteins form a complex to find and repair these mistakes. The process of proof-reading and restoring the DNA to the correct sequence is called mismatch repair (MMR). In Lynch syndrome, one or more of the proteins involved in MMR is mutated, and the mistakes in the DNA do not get corrected. The accumulation of these mistakes or mutations leads to cancer. Mutations in MMR proteins are not only found in familial cases of CRC, but also in patients with sporadic CRC. DNA repair machinery in the cell is important in keeping the genome stable and accurate. Defects in MMR also contribute to microsatellite instability (MIS), described above.

Testing for the mutations and genomic conditions that contribute to the development or progression of CRC are available at MGH in the sophisticated CLIA certified genomic testing lab, and in other large Centers and some private testing companies used by physicians. Validated treatments as well as clinical trials investigating improved targeted and immunologic therapies are available to patients at MGH.

NIH/NCI Cancer Website www.cancer.gov 2017
Genetic Alterations in CRC; Gastrointestinal Cancer Research; Amaghany T, et al.
Colorectal Cancer (CRC) is cancer that initiates in the colon or rectum-the lower part of the digestive system in the body. During digestion, food moves through the stomach and small intestine into the colon. The colon absorbs water and nutrients from food, and stores waste matter (stool) that moves from the colon through the rectum before leaving the body.

Most CRC's and rectal cancers are adenocarcinomas, meaning that they originate in cells that make and release mucus and other fluids. CRC often begins as a growth called a polyp, which may form on the inner wall of the colon or rectum. Over time, some polyps become cancerous. This highlights the importance of colonoscopy screening to find and remove polyps before they become cancerous.

CRC is the fourth most common type of cancer diagnosed in the U.S. Deaths from CRC have decreased with the use of colonoscopies and fecal occult blood tests, which check for blood in the stool. Disparities in survival have been observed between African American and other populations. This may be due to factors such as access to colonoscopy screening, or to other factors not yet identified.

Because of its prevalence, scientists have studied CRC extensively, even creating models of how cancer develops using CRC as an example. There are also families with a very high incidence of CRC occurrence. When these families were studied, certain conditions that create instability in the whole genome were identified that predispose people to CRC. These include what is called the chromosomal instability pathway (CIN) as well as microsatellite instability pathway (MSI). Both of these are recognized pathways in the development of CRC. These types of genetic instability lead to activation of proto-oncogenes such as KRAS, and the inactivation of tumor suppressors mentioned below.

Other genetic alterations in how the DNA in cells is organized have been found to contribute to CRC in families and individuals. These are called epigenetic changes. Normal DNA has methyl groups added in specific regions that regulate gene expression. When the genes that suppress growth-called tumor suppressors-are methylated in abnormal patterns, this prevents the production of tumor suppressor proteins that are important in controlling or stopping cell growth. When these are missing, unregulated growth occurs, contributing to the development of cancer. Some tumor suppressor proteins that are frequently inactivated in CRC are APC, TP53, and loss of one arm of chromosome 18 that contains a tumor suppressor.

The study of families with a high prevalence of CRC have lead scientists to discover genetic changes that contribute to the development of CRC in sporadic cases occurring in patients. Mutations in the genes encoding the following proteins have now been associated with subsets of CRC; AKT, APC, beta-catenin, BRAF, EGFR, ERBB2, ERBB3, IDH2, KRAS, NRAS, PIk3CA, PTEN, TP53,TRK 1, 2 and 3, and others still being identified.

Finally, distinct familial syndromes of CRC such as Lynch syndrome have been studied, and in these patients, the normal proof-reading of DNA during cell replication is found to be deficient. While DNA polymerase enzyme is replicating DNA before cells divide (with both daughter cells having a full complement of DNA), it occasionally makes errors. In a process of proof-reading behind this enzyme, several proteins form a complex to find and repair these mistakes. The process of proof-reading and restoring the DNA to the correct sequence is called mismatch repair (MMR). In Lynch syndrome, one or more of the proteins involved in MMR is mutated, and the mistakes in the DNA do not get corrected. The accumulation of these mistakes or mutations leads to cancer. Mutations in MMR proteins are not only found in familial cases of CRC, but also in patients with sporadic CRC. DNA repair machinery in the cell is important in keeping the genome stable and accurate. Defects in MMR also contribute to microsatellite instability (MIS), described above.

Testing for the mutations and genomic conditions that contribute to the development or progression of CRC are available at MGH in the sophisticated CLIA certified genomic testing lab, and in other large Centers and some private testing companies used by physicians. Validated treatments as well as clinical trials investigating improved targeted and immunologic therapies are available to patients at MGH.

NIH/NCI Cancer Website www.cancer.gov 2017
Genetic Alterations in CRC; Gastrointestinal Cancer Research; Amaghany T, et al.
Colorectal Cancer (CRC) is cancer that initiates in the colon or rectum-the lower part of the digestive system in the body. During digestion, food moves through the stomach and small intestine into the colon. The colon absorbs water and nutrients from food, and stores waste matter (stool) that moves from the colon through the rectum before leaving the body.

Most CRC's and rectal cancers are adenocarcinomas, meaning that they originate in cells that make and release mucus and other fluids. CRC often begins as a growth called a polyp, which may form on the inner wall of the colon or rectum. Over time, some polyps become cancerous. This highlights the importance of colonoscopy screening to find and remove polyps before they become cancerous.

CRC is the fourth most common type of cancer diagnosed in the U.S. Deaths from CRC have decreased with the use of colonoscopies and fecal occult blood tests, which check for blood in the stool. Disparities in survival have been observed between African American and other populations. This may be due to factors such as access to colonoscopy screening, or to other factors not yet identified.

Because of its prevalence, scientists have studied CRC extensively, even creating models of how cancer develops using CRC as an example. There are also families with a very high incidence of CRC occurrence. When these families were studied, certain conditions that create instability in the whole genome were identified that predispose people to CRC. These include what is called the chromosomal instability pathway (CIN) as well as microsatellite instability pathway (MSI). Both of these are recognized pathways in the development of CRC. These types of genetic instability lead to activation of proto-oncogenes such as KRAS, and the inactivation of tumor suppressors mentioned below.

Other genetic alterations in how the DNA in cells is organized have been found to contribute to CRC in families and individuals. These are called epigenetic changes. Normal DNA has methyl groups added in specific regions that regulate gene expression. When the genes that suppress growth-called tumor suppressors-are methylated in abnormal patterns, this prevents the production of tumor suppressor proteins that are important in controlling or stopping cell growth. When these are missing, unregulated growth occurs, contributing to the development of cancer. Some tumor suppressor proteins that are frequently inactivated in CRC are APC, TP53, and loss of one arm of chromosome 18 that contains a tumor suppressor.

The study of families with a high prevalence of CRC have lead scientists to discover genetic changes that contribute to the development of CRC in sporadic cases occurring in patients. Mutations in the genes encoding the following proteins have now been associated with subsets of CRC; AKT, APC, beta-catenin, BRAF, EGFR, ERBB2, ERBB3, IDH2, KRAS, NRAS, PIk3CA, PTEN, TP53,TRK 1, 2 and 3, and others still being identified.

Finally, distinct familial syndromes of CRC such as Lynch syndrome have been studied, and in these patients, the normal proof-reading of DNA during cell replication is found to be deficient. While DNA polymerase enzyme is replicating DNA before cells divide (with both daughter cells having a full complement of DNA), it occasionally makes errors. In a process of proof-reading behind this enzyme, several proteins form a complex to find and repair these mistakes. The process of proof-reading and restoring the DNA to the correct sequence is called mismatch repair (MMR). In Lynch syndrome, one or more of the proteins involved in MMR is mutated, and the mistakes in the DNA do not get corrected. The accumulation of these mistakes or mutations leads to cancer. Mutations in MMR proteins are not only found in familial cases of CRC, but also in patients with sporadic CRC. DNA repair machinery in the cell is important in keeping the genome stable and accurate. Defects in MMR also contribute to microsatellite instability (MIS), described above.

Testing for the mutations and genomic conditions that contribute to the development or progression of CRC are available at MGH in the sophisticated CLIA certified genomic testing lab, and in other large Centers and some private testing companies used by physicians. Validated treatments as well as clinical trials investigating improved targeted and immunologic therapies are available to patients at MGH.

NIH/NCI Cancer Website www.cancer.gov 2017
Genetic Alterations in CRC; Gastrointestinal Cancer Research; Amaghany T, et al.
PubMed ID's
2188735,
Expand Collapse Beta-Catenin (CTNNB1)  - General Description
CLICK IMAGE FOR MORE INFORMATION
The CTNNB1 gene encodes a protein called beta-catenin that has several important functions in the cell. These include being involved in cell to cell contacts at adherens junctions, and being involved in the WNT signaling pathway.

The first role beta-catenin is integral to is in participating in cell to cell contacts. Where cells are in contact with one another, beta catenin is part of a complex of proteins that form what are called adherens junctions. Adherens junctions are protein complexes that occur at cell-to-cell junctions and are essential for the formation and maintenance of epithelial cell layers. In this role, beta-catenin functions to anchor the actin cytoskeleton of cells, and to transmit the contact inhibition signal that causes cells to stop dividing once the epithelial layer of cells is complete. Beta catenin also has a role in cell migration.

In a second role, beta-catenin is involved in the Wnt signaling pathway (see graphic above). In the absence of a Wnt signal, beta catenin is normally kept at very low levels within the cell by a destruction complex. This destruction complex includes proteins called GSK-3, APC, and axin, and is responsible for degrading beta catenin. When a Wnt ligand binds to a Wnt receptor on the cell surface, this triggers a signal in the cell that causes the dissociation of the destruction complex, and beta catenin is no longer degraded. Instead, it builds up in the cytoplasm of the cell, and binds to T cell factor (TCF). Beta catenin/TCF translocate into the nucleus, and bind to Wnt target genes that promote growth, including C-Myc and Cyclin D1.

Mutations in the CTNNB1 gene that encodes the beta catenin protein result in the abnormal accumulation of the beta catenin protein in the cell. These and are frequently found in some cancers including colorectal cancer, endometrial and uterine cancers, as well as medulloblastomas. Mutations in CTNNB1/the beta catenin protein also occur in adenocarcinoma of the lung and colorectal cancers, and less frequently in liver cancer, gastric adenocarcinoma, bladder cancer, desmoid tumors, and pilomatrixoma.

Source: TumorPortal.org
The CTNNB1 gene encodes a protein called beta-catenin that has several important functions in the cell. These include being involved in cell to cell contacts at adherens junctions, and being involved in the WNT signaling pathway.

The first role beta-catenin is integral to is in participating in cell to cell contacts. Where cells are in contact with one another, beta catenin is part of a complex of proteins that form what are called adherens junctions. Adherens junctions are protein complexes that occur at cell-to-cell junctions and are essential for the formation and maintenance of epithelial cell layers. In this role, beta-catenin functions to anchor the actin cytoskeleton of cells, and to transmit the contact inhibition signal that causes cells to stop dividing once the epithelial layer of cells is complete. Beta catenin also has a role in cell migration.

In a second role, beta-catenin is involved in the Wnt signaling pathway (see graphic above). In the absence of a Wnt signal, beta catenin is normally kept at very low levels within the cell by a destruction complex. This destruction complex includes proteins called GSK-3, APC, and axin, and is responsible for degrading beta catenin. When a Wnt ligand binds to a Wnt receptor on the cell surface, this triggers a signal in the cell that causes the dissociation of the destruction complex, and beta catenin is no longer degraded. Instead, it builds up in the cytoplasm of the cell, and binds to T cell factor (TCF). Beta catenin/TCF translocate into the nucleus, and bind to Wnt target genes that promote growth, including C-Myc and Cyclin D1.

Mutations in the CTNNB1 gene that encodes the beta catenin protein result in the abnormal accumulation of the beta catenin protein in the cell. These and are frequently found in some cancers including colorectal cancer, endometrial and uterine cancers, as well as medulloblastomas. Mutations in CTNNB1/the beta catenin protein also occur in adenocarcinoma of the lung and colorectal cancers, and less frequently in liver cancer, gastric adenocarcinoma, bladder cancer, desmoid tumors, and pilomatrixoma.

Source: TumorPortal.org
PubMed ID's
19619488, 22682243
Expand Collapse Beta-Catenin (CTNNB1)  in Colorectal Cancer
New information on cancer, genes, and mutations is being discovered each day. Currently, researchers have not found any information on the gene and disease you have chosen. Please check back as new data may be available soon.
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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 30 Per Page:
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Protocol # Title Location Status Match
NCT02335918 A Dose Escalation and Cohort Expansion Study of Anti-CD27 (Varlilumab) and Anti-PD-1 (Nivolumab) in Advanced Refractory Solid Tumors A Dose Escalation and Cohort Expansion Study of Anti-CD27 (Varlilumab) and Anti-PD-1 (Nivolumab) in Advanced Refractory Solid Tumors MGH Open D
NCT02279433 A First-in-human Study to Evaluate the Safety, Tolerability and Pharmacokinetics of DS-6051b A First-in-human Study to Evaluate the Safety, Tolerability and Pharmacokinetics of DS-6051b MGH Open D
NCT02715284 A Phase 1 Dose Escalation and Cohort Expansion Study of TSR-042, an Anti-PD-1 Monoclonal Antibody, in Patients With Advanced Solid Tumors A Phase 1 Dose Escalation and Cohort Expansion Study of TSR-042, an Anti-PD-1 Monoclonal Antibody, in Patients With Advanced Solid Tumors MGH Open D
NCT02099058 A Phase 1/1b Study With ABBV-399, an Antibody Drug Conjugate, in Subjects With Advanced Solid Cancer Tumors A Phase 1/1b Study With ABBV-399, an Antibody Drug Conjugate, in Subjects With Advanced Solid Cancer Tumors MGH Open D
NCT02327169 A Phase 1B Study of MLN2480 in Combination With MLN0128 or Alisertib, or Paclitaxel, or Cetuximab, or Irinotecan in Adult Patients With Advanced Nonhematologic Malignancies A Phase 1B Study of MLN2480 in Combination With MLN0128 or Alisertib, or Paclitaxel, or Cetuximab, or Irinotecan in Adult Patients With Advanced Nonhematologic Malignancies MGH Open D
NCT01714739 A Study of an Anti-KIR Antibody in Combination With an Anti-PD1 Antibody in Patients With Advanced Solid Tumors A Study of an Anti-KIR Antibody in Combination With an Anti-PD1 Antibody in Patients With Advanced Solid Tumors MGH Open D
NCT01633970 A Study of Atezolizumab Administered in Combination With Bevacizumab and/or With Chemotherapy in Participants With Locally Advanced or Metastatic Solid Tumors A Study of Atezolizumab Administered in Combination With Bevacizumab and/or With Chemotherapy in Participants With Locally Advanced or Metastatic Solid Tumors MGH Open D
NCT02467361 A Study of BBI608 Administered in Combination With Immune Checkpoint Inhibitors in Adult Patients With Advanced Cancers A Study of BBI608 Administered in Combination With Immune Checkpoint Inhibitors in Adult Patients With Advanced Cancers MGH Open D
NCT02228811 A Study of DCC-2701 in Participants With Advanced Solid Tumors A Study of DCC-2701 in Participants With Advanced Solid Tumors MGH Open D
NCT01351103 A Study of LGK974 in Patients With Malignancies Dependent on Wnt Ligands A Study of LGK974 in Patients With Malignancies Dependent on Wnt Ligands MGH Open D
Trial Status: Showing Results: 1-10 of 30 Per Page:
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