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CTNNB1
Variants
VariantGeneTypeCOSMIC IDDNA Change (Coding Nucleotide)Exon
CTNNB1 codon(s) 32, 33, 34, 35, 36, 37, 41, 45 anyCTNNB1any3, 3, 3, 3, 3, 3, 3, 3
CTNNB1 S45PCTNNB1missense3
CTNNB1 G34ECTNNB1missense3
CTNNB1 S37CCTNNB1missense3
CTNNB1 S37FCTNNB1missense3
CTNNB1 D32VCTNNB1missense3
CTNNB1 codon(s) 41, 45 anyCTNNB1any3, 3
CTNNB1 S37YCTNNB1missense3
CTNNB1 copy number gainCTNNB1CNV
CTNNB1 copy number lossCTNNB1CNV
CTNNB1 any mutationCTNNB1any
CTNNB1 Y30_I35delCTNNB1deletion3
CTNNB1 S33FCTNNB1missenseCOSM56693
CTNNB1 T41ACTNNB1missense3
CTNNB1 S45FCTNNB1missense3

Interpretations

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Tier 1
CTNNB1
Variants
CTNNB1 codon(s) 32, 33, 34, 35, 36, 37, 41, 45 any
CTNNB1 S45P
CTNNB1 G34E
CTNNB1 S37C
CTNNB1 S37F
CTNNB1 D32V
CTNNB1 codon(s) 41, 45 any
CTNNB1 S37Y
Primary Sites
Blood
Bone Marrow
Tumor Types
Myelodysplastic Syndrome
Acute Myeloid Leukemia
Interpretation

Beta catenin is a transcriptional co-regulator and an adapter protein for cellular adhesion; it comprises part of the Wnt signaling pathway and intracellular levels of beta-catenin are regulated by its phosphorylation, ubiquitination and proteosomal degradation. Accumulation of nuclear beta catenin can lead to a tumoral phenotype and oncogenic transformation in a variety of solid tumors. Various oncogenic mutants of beta catenin have been found in different tumor types which alter its degradation, leading to its accumulation and promoting tumor growth. Some of these mutations are located at the N-terminus of the protein at the sites of phosphorylation which normally regulate its degradation. Interestingly, in a recent study, 38% of patients with myelodysplastic syndromes or acute myeloid leukaemia, showed increased β-catenin signalling and nuclear accumulation of beta catenin in osteoblasts was associated with increased Notch signalling in haematopoietic cells consistent with a model where abnormalities of osteolineage cells are associated with myeloid malignancies. In addition, aberrant Wnt siganling has been reported to play a role in chronic myeloid leukemia, acute lymphoblastic leukemia and non-hodgkin lymphomas. Inhibition of beta catenin using small molecule inhibitors is currently being investigated in various tumor types. Recent studies suggest that targeting of the Wnt pathway and beta catenin may be promising targets in the therapy of acute myeloid leukemia.

Last updated: 2016-06-04 21:23:20 UTC
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Tier 3
CTNNB1
Variants
CTNNB1 codon(s) 32, 33, 34, 35, 36, 37, 41, 45 any
Primary Sites
Skin
Tumor Types
Melanoma
Interpretation

Somatic mutations in CTNNB1 (Beta-catenin) have been found in ~2-3% of malignant melanomas. Preclinical models have demonstrated that concurrent mutations in Beta-catenin and NRAS are synergistic in promoting melanoma formation.

Last updated: 2020-07-24 14:51:09 UTC
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Tier 2
CTNNB1
Variants
CTNNB1 S45P
Primary Sites
Lung
Tumor Types
Adenocarcinoma
Interpretation

CTNNB1 encodes the protein b-catenin, a transcriptional activator involved in the WNT signaling pathway. Somatic gain-of-function mutations in CTNNB1 result in aberrant accumulation of the b-catenin protein and are prevalent in a wide range of solid tumors, including endometrial carcinoma, ovarian carcinoma, hepatocellular carcinoma, and colorectal carcinoma, among others. Genetic alterations in CTNNB1 have been identified in 4% of non-small cell lung cancers. The CTNNB1 S45P mutation is likely oncogenic, but no real progress has been made in targeting oncogenic mutant forms of CTNNB1 in lung cancer. However, CTNNB1 mutation-positive cancers are presumed to be resistant to pharmacologic inhibition of upstream components of the WNT pathway, instead requiring direct inhibition of b-catenin function. In one study pharmacological inhibition of b-catenin suppressed EGFR-L858R/T790M mutated lung tumor and genetic deletion of the b-catenin gene dramatically reduced lung tumor formation in transgenic mice, suggesting that b-catenin plays an essential role in lung tumorigenesis and that targeting the b-catenin pathway may provide novel strategies to prevent lung cancer development or overcome resistance to EGFR TKIs. These results should be interpreted in the clinical context.

Last updated: 2019-01-22 18:31:14 UTC
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Tier 2
CTNNB1
Variants
CTNNB1 codon(s) 41, 45 any
Primary Sites
Chest Wall
Tumor Types
Fibromatosis
Interpretation

CTNNB1 mutations are highly prevalent and were detected in 84 to 87% of all sporadic fibromatosis/desmoid tumors. Most CTNNB1 mutations in fibromatosis/desmoid tumors are predominantly missense mutations in codons 41 and 45 of exon 3. These mutations result in β-catenin stabilization, increased nuclear accumulation and activation of the Wnt signaling pathway. Specific CTNNB1 mutations have been reported to predict recurrence in some cases of extra-abdominal and abdominal aggressive fibromatosis. A S45F mutation increased the risk of recurrence significantly.

Last updated: 2016-06-07 01:55:04 UTC
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Tier 2
CTNNB1
Variants
CTNNB1 S37Y
CTNNB1 codon(s) 32, 33, 34, 35, 36, 37, 41, 45 any
Primary Sites
Brain
Spinal Cord
Brain, Supratentorial
Brain, Infratentorial
Tumor Types
Craniopharyngioma
Interpretation

Mutations in beta catenin (CTNNB1) are seen in about 90% of adamantinomatous craniopharyngiomas and mutations in BRAF (V600E) in papillary craniopharyngiomas. Adamantinomatous and papillary craniopharyngiomas have been shown to carry clonal mutations that are mutually exclusive. These findings indicate that the adamantinomatous and papillary subtypes have distinct molecular underpinnings, each principally driven by mutations in a single well-established oncogene - CTNNB1 in the adamantinomatous form and BRAF in the papillary form, independent of age. This may have implications for the diagnosis and treatment of these tumors.

Last updated: 2020-07-24 14:51:45 UTC
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Tier 3
CTNNB1
Variants
CTNNB1 codon(s) 32, 33, 34, 35, 36, 37, 41, 45 any
Primary Sites
Uterus
Tumor Types
Sarcoma
Interpretation

Beta catenin is a transcriptional co-regulator and an adapter protein for cellular adhesion; it comprises part of the Wnt signaling pathway and intracellular levels of beta-catenin are regulated by its phosphorylation, ubiquitination and proteosomal degradation. Accumulation of nuclear beta catenin can lead to a tumoral phenotype and oncogenic transformation in a variety of solid tumors. Various oncogenic mutants of beta catenin have been found in different tumor types which alter its degradation, leading to its accumulation and promoting tumor growth. Mutations in exon 3 of CTNNB1 result in stabilization of a protein that resists degradation, leading to nuclear accumulation of b-catenin, have been described in endometrioid endometrial carcinoma. The reported frequency of CTNNB1 mutations in endometrioid endometrial carcinoma ranges from 14-44%. However, these mutations are not described previously in endometrial sarcomas. Of note, CTNNB1 mutations are highly common in desmoid fibromatosis.

Last updated: 2020-07-24 14:51:24 UTC
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Tier 2
CTNNB1
Variants
CTNNB1 codon(s) 41, 45 any
Primary Sites
Colon
Rectum
Tumor Types
Adenocarcinoma
Interpretation

Beta catenin is a transcriptional co-regulator and an adapter protein for cellular adhesion; it comprises part of the Wnt signaling pathway and intracellular levels of beta-catenin are regulated by its phosphorylation, ubiquitination and proteosomal degradation. Accumulation of nuclear beta catenin can lead to a tumoral phenotype and oncogenic transformation in a variety of solid tumors. Various oncogenic mutants of beta catenin have been found in different tumor types which alter its degradation, leading to its accumulation and promoting tumor growth. CTNNB1 mutations are particularly common in colorectal carcinomas associated with hereditary non-polyposis colon cancer syndrome and wild type APC gene, and are extremely rare in sporadic colorectal cancers. These mutations consist almost entirely of transitions at codons 41 and 45, and result in stabilization of a protein that resists degradation, leading to nuclear accumulation of β-catenin. Up to 50% of primary colorectal carcinomas with CTNNB1 mutations exhibit microsatellite instability, suggesting that CTNNB1 mutations may be more common in the DNA mismatch repair pathway of tumorigenesis. Microsatellite instability is generally associated with better prognosis when compared to patients with intact mismatch repair pathways. Preclinical studies suggest that CTNNB1 mutations may confer resistance to PI3K-AKT inhibitors in colorectal cancer.

Last updated: 2016-05-04 16:10:00 UTC
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Tier 3
CTNNB1
Variants
Primary Sites
Prostate
Tumor Types
Adenocarcinoma
Interpretation

Beta catenin is a transcriptional co-regulator and an adapter protein for cellular adhesion; it comprises part of the Wnt signaling pathway and intracellular levels of beta-catenin are regulated by its phosphorylation, ubiquitination and proteosomal degradation. Accumulation of nuclear beta catenin can lead to a tumoral phenotype and oncogenic transformation in a variety of solid tumors. Various oncogenic mutants of beta catenin have been found in different tumor types which alter its degradation, leading to its accumulation and promoting tumor growth. CTNNB1 mutations in prostate cancer occur rarely, in only 2-5% of cases. Currently, the function of β-Catenin in human prostate cancer continues to be explored. In the context of prostate, β-Catenin may modulate the androgen receptor (AR) pathway. Some preclinical mouse studies have shown that increased β-Catenin levels can cooperate with PTEN loss to promote the progression of aggressive invasive prostate cancer together with squamous metaplasia. Clinical correlation is recommended.

Last updated: 2016-05-05 13:29:28 UTC
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Tier 3
CTNNB1
Variants
Primary Sites
Lung
Tumor Types
Non-Small Cell Lung Carcinoma
Interpretation

The cytoplasmic β-catenin protein is implicated as a cell-cell adhesion regulator coupled with cadherin and is considered as a member in the wingless/Wnt signal transduction pathway. Mutations in CTNNB1, the gene encoding β-catenin, tend to impact or even eliminate APC-dependent serine and threonine phosphorylation sites in exon 3, resulting in oncogenic stabilization of the protein. Increased protein within the nuclei serves as a transcriptional factor through binding to the Tcf/Lef family. Mutations in the β-catenin gene are uncommon in NSCLC occurring in about 1-4% of the cases. Nuclear accumulation of β-catenin was found to be associated with EGFR mutations, and β-catenin overexpression was associated with NSCLC cell line resistance to gefitinib. Wnt pathway inhibitors are in preclinical development or have entered early clinical trials. Because high β-catenin expression has been associated with good outcome rather than with poor outcome in NSCLC patients, it could potentially prove important to target specific downstream β-catenin functions rather than using agents that could directly suppress β-catenin levels through upstream targeting of the Wnt pathway.

Last updated: 2016-08-01 19:47:33 UTC
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Tier 2
CTNNB1
Variants
CTNNB1 copy number gain
CTNNB1 copy number loss
Primary Sites
Adrenal Gland
Anus
Ampulla (Pancreaticobiliary Duct)
Appendix
Bladder
Blood
Bone
Bone Marrow
Brain
Breast
Spinal Cord
Cervix
Chest Wall
Colon
Endometrium
Esophagus
Eye
Fallopian Tube
Fibroadipose Tissue
Gall Bladder
Kidney
Larynx
Liver
Lung
Lymph Node
Nasal Cavity
Oral Cavity
Ovary
Pancreas
Parathyroid
Penis
Peripheral Nervous System
Peritoneum
Pharynx
Pituitary
Placenta
Pleura
Prostate
Retroperitoneum
Salivary Gland
Seminal Vesicle
Skeletal Muscle
Skin
Small Intestine
Soft Tissue
Spleen
Stomach
Testis
Thymus
Thyroid
Tonsil
Unknown
Ureter
Uterus
Vagina
Rectum
Cartilage
Blood Vessel
Buccal Swab
Heart
Trachea
Salivary Duct
Spermatic Cord
Vulva
Brain, Infratentorial
Brain, Supratentorial
Gastroesophageal Junction
Sellar
Suprasellar
Peritoneal fluid
Pleural Fluid
Tongue
Tumor Types
Acinar Cell Carcinoma
Acinic Cell Carcinoma
Acute Myeloid Leukemia
Adenocarcinoma
Adenoid Cystic Carcinoma
Adenosarcoma
Ameloblastic Tumor
Anaplastic Large Cell Lymphoma
Angioimmunoblastic T-Cell Lymphoma
Angiomatoid Fibrous Histiocytoma
Angiomatosis
Angiomyolipoma
Angiosarcoma
Astrocytoma, Anaplastic
Atypical Chronic Myeloid Leukemia
B Lymphoblastic Leukemia/Lymphoma
Basal Cell Carcinoma
Burkitt Lymphoma
Carcinoid Tumor
Carcinoma
Carcinosarcoma
Cholangiocarcinoma
Chondrosarcoma
Chordoma
Choriocarcinoma
Chromophobe Renal Cell Carcinoma
Chronic Lymphocytic Leukemia
Chronic Myeloid Leukemia
Chronic Myelomonocytic Leukemia
Chronic Neutrophilic Leukemia
Classical Hodgkin Lymphoma
Clear Cell Carcinoma
Clear Cell Renal Cell Carcinoma
Craniopharyngioma
Dermatofibrosarcoma
Desmoplastic Small Round Cell Tumor
Diffuse Large B Cell Lymphoma
Ductal Carcinoma
Ependymoma
Essential Thrombocythemia
Ewing Sarcoma
Fibromatosis
Follicular Carcinoma
Follicular Lymphoma
Gastrointestinal Stromal Tumor
Germ Cell Tumor
Giant Cell Tumor
Glioblastoma
Glomus Tumor
Granular Cell Tumor
Hairy Cell Leukemia
Hemangioendothelioma
Hepatocellular Carcinoma
Histiocytic and Dendritic Cell Neoplasms
Invasive Ductal Carcinoma
Kaposi Sarcoma
Langerhans Cell Histiocytosis
Leiomyoma
Leiomyosarcoma
Lipoma
Liposarcoma
Lobular Carcinoma
Lymphoplasmacytic Lymphoma
Malignant Mullerian Mixed Tumor
Mantle Cell Lymphoma
Marginal Zone B Cell Lymphoma
Mast Cell Neoplasm
MDS with Ring Sideroblasts
Medullary Carcinoma
Medulloblastoma
Melanoma
Meningioma
Merkel Cell Carcinoma
Mesothelioma
Mucinous Adenocarcinoma
Mucinous Tumors of Ovary
Mucoepidermoid Carcinoma
Myelodysplastic Syndrome
Myeloproliferative Neoplasm
Myxofibrosarcoma
Nasopharyngeal Carcinoma
Neuroblastoma
Neuroendocrine Carcinoma
Neuroendocrine Neoplasm
NK Cell Lymphoproliferative Disorder
NLPHL
Non-Small Cell Lung Carcinoma
Oligodendroglioma
Osteosarcoma
Papillary Carcinoma
Papillary Renal Cell Carcinoma
Peripheral T Cell Lymphoma
Pheochromocytoma
Plasma Cell Disorder
Polycythemia Vera
Post-Transplant Lymphoproliferative Disorder
Primary Myelofibrosis
Primitive Neuroectodermal Tumor
Renal Cell Carcinoma
Reninoma
Retinoblastoma
Rhabdomyosarcoma
Sarcoma
Schwannoma
Serous Carcinoma
Sex Cord Stromal Tumor
Small Cell Carcinoma
Solid Pseudopapillary Tumor of Pancreas
Spindle Cell Neoplasm
Squamous Cell Carcinoma
T Cell Lymphoproliferative Disorder
T Lymphoblastic Leukemia/Lymphoma
T-Cell LGL Leukemia
Thymic Carcinoma
Thymoma
Urothelial Carcinoma
Tumors of Peripheral Nerves
Unknown
Wilms Tumor
Ependymoma, Anaplastic
Astrocytoma, Pilocytic
Ganglioglioma
Neuroepithelial Neoplasm, NOS
Pleomorphic Carcinoma
Solitary Fibrous Tumor
Neuroepithelial neoplasm, high grade
Leukocytosis
Thrombocytosis
Monocytosis
Cytopenia
Other Acute Leukemia
Astrocytoma, NOS
Acute Leukemia of Unspecified Cell Type
Anemia, Unspecified
Astrocytoma, Diffusely Infiltrating
Diffuse Midline Glioma
Infiltrating Glioma, NOS
Intraductal Papillary Mucinous Neoplasm (IPMN)
Leukopenia
Lymphadenopathy
Lymphocytosis, Symptomatic
Monoclonal Gammopathy
Mucinous or Serous Cystic Neoplasms of Pancreas
Mycosis Fungoides, Unspecified Site
Oligodendroglioma, Anaplastic
Pleomorphic Xanthoastrocytoma
Rash and Other Nonspecific Skin Eruption
Thrombocytopenia, Unspecified
Eosinophilia
Myelodysplastic/Myeloproliferative Neoplasm
Myeloid Neoplasm
Polycythemia
Hurthle Cell Carcinoma
High Grade Glioma
Undifferentiated Sarcoma
Glioma
Interpretation

This gene is a known cancer gene.

Last updated: 2018-05-17 15:39:18 UTC
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Tier 2
CTNNB1
Variants
CTNNB1 any mutation
Primary Sites
Adrenal Gland
Anus
Ampulla (Pancreaticobiliary Duct)
Appendix
Bladder
Blood
Bone
Bone Marrow
Brain
Breast
Spinal Cord
Cervix
Chest Wall
Colon
Endometrium
Esophagus
Eye
Fallopian Tube
Fibroadipose Tissue
Gall Bladder
Kidney
Larynx
Liver
Lung
Lymph Node
Nasal Cavity
Oral Cavity
Ovary
Pancreas
Parathyroid
Penis
Peripheral Nervous System
Peritoneum
Pharynx
Pituitary
Placenta
Pleura
Prostate
Retroperitoneum
Salivary Gland
Seminal Vesicle
Skeletal Muscle
Skin
Small Intestine
Soft Tissue
Spleen
Stomach
Testis
Thymus
Thyroid
Tonsil
Unknown
Ureter
Uterus
Vagina
Rectum
Cartilage
Blood Vessel
Buccal Swab
Heart
Trachea
Salivary Duct
Spermatic Cord
Vulva
Brain, Infratentorial
Brain, Supratentorial
Gastroesophageal Junction
Sellar
Suprasellar
Peritoneal fluid
Pleural Fluid
Tongue
Tumor Types
Acinar Cell Carcinoma
Acinic Cell Carcinoma
Acute Myeloid Leukemia
Adenocarcinoma
Adenoid Cystic Carcinoma
Adenosarcoma
Ameloblastic Tumor
Anaplastic Large Cell Lymphoma
Angioimmunoblastic T-Cell Lymphoma
Angiomatoid Fibrous Histiocytoma
Angiomatosis
Angiomyolipoma
Angiosarcoma
Astrocytoma, Anaplastic
Atypical Chronic Myeloid Leukemia
B Lymphoblastic Leukemia/Lymphoma
Basal Cell Carcinoma
Burkitt Lymphoma
Carcinoid Tumor
Carcinoma
Carcinosarcoma
Cholangiocarcinoma
Chondrosarcoma
Chordoma
Choriocarcinoma
Chromophobe Renal Cell Carcinoma
Chronic Lymphocytic Leukemia
Chronic Myeloid Leukemia
Chronic Myelomonocytic Leukemia
Chronic Neutrophilic Leukemia
Classical Hodgkin Lymphoma
Clear Cell Carcinoma
Clear Cell Renal Cell Carcinoma
Craniopharyngioma
Dermatofibrosarcoma
Desmoplastic Small Round Cell Tumor
Diffuse Large B Cell Lymphoma
Ductal Carcinoma
Ependymoma
Essential Thrombocythemia
Ewing Sarcoma
Fibromatosis
Follicular Carcinoma
Follicular Lymphoma
Gastrointestinal Stromal Tumor
Germ Cell Tumor
Giant Cell Tumor
Glioblastoma
Glomus Tumor
Granular Cell Tumor
Hairy Cell Leukemia
Hemangioendothelioma
Hepatocellular Carcinoma
Histiocytic and Dendritic Cell Neoplasms
Invasive Ductal Carcinoma
Kaposi Sarcoma
Langerhans Cell Histiocytosis
Leiomyoma
Leiomyosarcoma
Lipoma
Liposarcoma
Lobular Carcinoma
Lymphoplasmacytic Lymphoma
Malignant Mullerian Mixed Tumor
Mantle Cell Lymphoma
Marginal Zone B Cell Lymphoma
Mast Cell Neoplasm
MDS with Ring Sideroblasts
Medullary Carcinoma
Medulloblastoma
Melanoma
Meningioma
Merkel Cell Carcinoma
Mesothelioma
Mucinous Adenocarcinoma
Mucinous Tumors of Ovary
Mucoepidermoid Carcinoma
Myelodysplastic Syndrome
Myeloproliferative Neoplasm
Myxofibrosarcoma
Nasopharyngeal Carcinoma
Neuroblastoma
Neuroendocrine Carcinoma
Neuroendocrine Neoplasm
NK Cell Lymphoproliferative Disorder
NLPHL
Non-Small Cell Lung Carcinoma
Oligodendroglioma
Osteosarcoma
Papillary Carcinoma
Papillary Renal Cell Carcinoma
Peripheral T Cell Lymphoma
Pheochromocytoma
Plasma Cell Disorder
Polycythemia Vera
Post-Transplant Lymphoproliferative Disorder
Primary Myelofibrosis
Primitive Neuroectodermal Tumor
Renal Cell Carcinoma
Reninoma
Retinoblastoma
Rhabdomyosarcoma
Sarcoma
Schwannoma
Serous Carcinoma
Sex Cord Stromal Tumor
Small Cell Carcinoma
Solid Pseudopapillary Tumor of Pancreas
Spindle Cell Neoplasm
Squamous Cell Carcinoma
T Cell Lymphoproliferative Disorder
T Lymphoblastic Leukemia/Lymphoma
T-Cell LGL Leukemia
Thymic Carcinoma
Thymoma
Urothelial Carcinoma
Tumors of Peripheral Nerves
Unknown
Wilms Tumor
Ependymoma, Anaplastic
Astrocytoma, Pilocytic
Ganglioglioma
Neuroepithelial Neoplasm, NOS
Pleomorphic Carcinoma
Solitary Fibrous Tumor
Neuroepithelial neoplasm, high grade
Leukocytosis
Thrombocytosis
Monocytosis
Cytopenia
Other Acute Leukemia
Astrocytoma, NOS
Acute Leukemia of Unspecified Cell Type
Anemia, Unspecified
Astrocytoma, Diffusely Infiltrating
Diffuse Midline Glioma
Infiltrating Glioma, NOS
Intraductal Papillary Mucinous Neoplasm (IPMN)
Leukopenia
Lymphadenopathy
Lymphocytosis, Symptomatic
Monoclonal Gammopathy
Mucinous or Serous Cystic Neoplasms of Pancreas
Mycosis Fungoides, Unspecified Site
Oligodendroglioma, Anaplastic
Pleomorphic Xanthoastrocytoma
Rash and Other Nonspecific Skin Eruption
Thrombocytopenia, Unspecified
Eosinophilia
Myelodysplastic/Myeloproliferative Neoplasm
Myeloid Neoplasm
Polycythemia
Hurthle Cell Carcinoma
High Grade Glioma
Undifferentiated Sarcoma
Glioma
Interpretation

This gene is a known cancer gene.

Last updated: 2018-05-17 15:40:13 UTC
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Tier 2
CTNNB1
Variants
CTNNB1 G34E
Primary Sites
Pancreas
Tumor Types
Acinar Cell Carcinoma
Interpretation

Beta catenin is a transcriptional co-regulator and an adapter protein for cellular adhesion; it comprises part of the Wnt signaling pathway and intracellular levels of beta-catenin are regulated by its phosphorylation, ubiquitination and proteosomal degradation. Accumulation of nuclear beta catenin can lead to a tumoral phenotype and oncogenic transformation in a variety of solid tumors. Various oncogenic mutants of beta catenin have been found in different tumor types which alter its degradation, leading to its accumulation and promoting tumor growth. Alterations in genes coding for members of the APC/b (beta)-catenin pathway have been identified in 20--25% of acinar cell carcinomas. These included inactivating mutations in APC as well as activating mutations in CTNNB1. CTNNB1 alterations have been identified in approximately 9% of pancreatic acinar cell carcinomas. CTNNB1 G34E is a rare mutation and does not lie within any known functional domains of the CTNNB1 protein. One study has shown that this mutation results in resistance to degradation, leading to increased pathway activation. Preclinical studies in CTNNB1 mutated solid tumors are underway. The full clinicopathological significance of CTNNB1 G34E remains to be further elucidated in pancreatic acinar cell carcinoma.

Last updated: 2018-03-06 17:58:36 UTC
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Tier 2
CTNNB1
Variants
CTNNB1 Y30_I35del
Primary Sites
Lung
Tumor Types
Adenocarcinoma
Interpretation

The cytoplasmic b-catenin protein is implicated as a cell-cell adhesion regulator coupled with cadherin and is considered as a member in the wingless/Wnt signal transduction pathway. Mutations in CTNNB1, the gene encoding b-catenin, tend to impact or even eliminate APC-dependent serine and threonine phosphorylation sites in exon 3, resulting in oncogenic stabilization of the protein. Mutations in the b-catenin gene are uncommon in NSCLC occurring in about 1-4% of the cases. This particular variant has not been described lung adenocarcinomas but is located in a hotspot, thus likely to be oncogenic. Clinical correlation is recommended.

Last updated: 2018-10-05 18:21:13 UTC
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Tier 2
CTNNB1
Variants
CTNNB1 S45F
Primary Sites
Soft Tissue
Tumor Types
Unknown
Interpretation

CTNNB1 encodes the protein b-catenin, a transcriptional activator involved in the WNT signaling pathway. Somatic gain-of-function mutations in CTNNB1 result in aberrant accumulation of the b-catenin protein and are prevalent in a wide range of solid tumors, including endometrial carcinoma, ovarian carcinoma, hepatocellular carcinoma, and colorectal carcinoma, among others. Cancers with CTNNB1 mutations are presumed to be resistant to pharmacologic inhibition of upstream components of the WNT pathway, instead requiring direct inhibition of b-catenin function. Genetic alterations in CTNNB1 have been identified in 4% of non-small cell lung cancers. The CTNNB1 S45F mutation is likely oncogenic. No real progress has been made in targeting oncogenic mutant forms of CTNNB1 in lung cancer.

Last updated: 2019-01-22 18:32:05 UTC
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Tier 2
CTNNB1
Variants
CTNNB1 T41A
Primary Sites
Ampulla (Pancreaticobiliary Duct)
Tumor Types
Adenocarcinoma
Interpretation

CTNNB1 encodes b-catenin, a transcriptional co-regulator and an adapter protein for cellular adhesion involved in the WNT signaling pathway. Somatic gain-of-function mutations in CTNNB1 result in aberrant accumulation of the b-catenin protein and are prevalent in a wide range of solid tumors, including uterine/endometrial carcinoma, ovarian, hepatocellular carcinoma, and colorectal carcinoma, among others. CTNNB1 mutations are particularly common in colorectal carcinomas associated with hereditary non-polyposis colon cancer syndrome and wild type APC gene, and are extremely rare in sporadic colorectal cancers. CTNNB1 is altered in 2.9% of pancreatic adenocarcinomas. The CTNNB1 T41A mutation is known to be oncogenic. Preclinical studies suggest that CTNNB1 mutations may confer resistance to PI3K-AKT inhibitors in colorectal cancer. Cancers with CTNNB1 mutations are presumed to be resistant to pharmacologic inhibition of upstream components of the WNT pathway, instead requiring direct inhibition of b-catenin function. The role of CTNNB1 mutations in pancreatic adenocarcinomas requires further elucidation.

Last updated: 2019-01-22 18:49:51 UTC
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Tier 2
CTNNB1
Variants
CTNNB1 S33F
Primary Sites
Prostate
Tumor Types
Adenocarcinoma
Interpretation

Beta catenin is a transcriptional co-regulator and an adapter protein for cellular adhesion; it comprises part of the Wnt signaling pathway and intracellular levels of beta-catenin are regulated by its phosphorylation, ubiquitination and proteosomal degradation. Accumulation of nuclear beta catenin can lead to a tumoral phenotype and oncogenic transformation in a variety of solid tumors. Various oncogenic mutants of beta catenin have been found in different tumor types which alter its degradation, leading to its accumulation and promoting tumor growth. CTNNB1 mutations in prostate cancer occur rarely, in only 2-5% of cases. Currently, the function of b-Catenin in human prostate cancer continues to be explored. In the context of prostate, b-Catenin may modulate the androgen receptor (AR) pathway. This particular variant S33F is predicted to confer a gain of function to the CTNNB1 protein as demonstrated by nuclear accumulation of CTNNB1. Clinical correlation is recommended.

Last updated: 2019-01-22 19:23:08 UTC
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Tier 2
CTNNB1
Variants
CTNNB1 S37C
Primary Sites
Lung
Tumor Types
Adenocarcinoma
Interpretation

The cytoplasmic b-catenin protein is implicated as a cell-cell adhesion regulator coupled with cadherin and is considered as a member in the wingless/Wnt signal transduction pathway. Mutations in CTNNB1, the gene encoding b-catenin, tend to impact or even eliminate APC-dependent serine and threonine phosphorylation sites in exon 3, resulting in oncogenic stabilization of the protein. Mutations in the b-catenin gene are uncommon in NSCLC occurring in about 1-4% of the cases. CTNNB1 S37C is a gain of function mutation, has been described in 0.3% of non-small cell lung carcinomas and is likely oncogenic. However, its prognostic and therapeutic significance remains to be fully elucidated.

Last updated: 2019-02-22 18:05:50 UTC
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Tier 2
CTNNB1
Variants
CTNNB1 S37F
Primary Sites
Lung
Tumor Types
Adenocarcinoma
Interpretation

CTNNB1 encodes the protein b-catenin, a transcriptional activator involved in the WNT signaling pathway. Somatic gain-of-function mutations in CTNNB1 result in aberrant accumulation of the b-catenin protein and are prevalent in a wide range of solid tumors, including endometrial carcinoma, ovarian carcinoma, hepatocellular carcinoma, and colorectal carcinoma, among others. Genetic alterations in CTNNB1 have been identified in 4% of non-small cell lung cancers. The CTNNB1 S437F mutation has been reported as pathogenic in lung adenocarcinoma, but no real progress has been made in targeting oncogenic mutant forms of CTNNB1 in lung cancer. However, CTNNB1 mutation-positive cancers are presumed to be resistant to pharmacologic inhibition of upstream components of the WNT pathway, instead requiring direct inhibition of b-catenin function. In one study pharmacological inhibition of b-catenin suppressed EGFR-L858R/T790M mutated lung tumor and genetic deletion of the b-catenin gene dramatically reduced lung tumor formation in transgenic mice, suggesting that b-catenin plays an essential role in lung tumorigenesis and that targeting the b-catenin pathway may provide novel strategies to prevent lung cancer development or overcome resistance to EGFR TKIs. These results should be interpreted in the clinical context.

Last updated: 2019-03-11 16:31:19 UTC
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When using PMKB, please cite: Huang et al., JAMIA 2017


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