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APC
Variants
VariantGeneTypeCOSMIC IDDNA Change (Coding Nucleotide)Exon
APC E1317QAPCmissense16
APC codon(s) 1464 frameshiftAPCframeshift16
APC Q1338*APCnonsense16
APC R1114*APCnonsense16
APC codon(s) 1556 frameshiftAPCframeshift16
APC R876*APCnonsense16
APC codon(s) 1465 frameshiftAPCframeshift16
APC codon(s) 1307 frameshiftAPCframeshift16
APC Q1429*APCnonsense16
APC any missenseAPCmissense
APC any nonsenseAPCnonsense
APC any frameshiftAPCframeshift
APC I1307KAPCmissenseCOSM266973920T>A16
APC copy number gainAPCCNV
APC copy number lossAPCCNV
APC any mutationAPCany
APC K1454EAPCmissense16

Interpretations

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Tier 2
APC
Variants
APC any missense
APC any nonsense
APC any frameshift
Primary Sites
Colon
Rectum
Tumor Types
Adenocarcinoma
Interpretation

Somatic APC mutations are common events in colorectal adenocarcinomas, reported in up to 76% of the cases. Loss of normal APC function is known to be an early event in both familial and sporadic colon cancer pathogenesis, occurring at the pre-adenoma stage. APC mutations do not appear to significantly affect the prognosis of colorectal cancer patients. While there are a number of small molecule inhibitors in development that target the Wnt pathway, there is currently no matched targeted therapy available for colorectal cancer patients harboring an APC mutation.

Last updated: 2017-03-15 21:09:57 UTC
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Tier 2
APC
Variants
APC codon(s) 1464 frameshift
APC Q1338*
APC R1114*
APC codon(s) 1556 frameshift
APC R876*
APC codon(s) 1465 frameshift
APC codon(s) 1307 frameshift
APC Q1429*
Primary Sites
Colon
Rectum
Tumor Types
Adenocarcinoma
Interpretation

Somatic APC mutations are common events in colorectal adenocarcinomas, reported in up to 76% of the cases. Loss of normal APC function is known to be an early event in both familial and sporadic colon cancer pathogenesis, occurring at the pre-adenoma stage. APC mutations do not significantly affect the prognosis of colorectal cancer patients. While there are a number of small molecule inhibitors in development that target the Wnt pathway, there is currently no matched targeted therapy available for colorectal cancer patients harboring an APC mutation.

Last updated: 2017-03-15 21:14:46 UTC
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Tier 3
APC
Variants
APC E1317Q
Primary Sites
Colon
Stomach
Thyroid
Rectum
Tumor Types
Adenocarcinoma
Carcinoma
Interpretation

Familial adenomatous polyposis (FAP) is a disease with autosomal-dominant inheritance that predisposes to carcinoma of the colorectum, stomach, duodenum, and thyroid. There is increasing evidence that germline variants in APC (E1317Q) predispose to the development of multiple colorectal adenomas and carcinoma.

Last updated: 2015-12-09 20:11:10 UTC
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Tier 3
APC
Variants
APC E1317Q
APC codon(s) 1307 frameshift
Primary Sites
Thyroid
Tumor Types
Papillary Carcinoma
Interpretation

Germline APC mutations are characteristically associated with Familial Adenomatous Polyposis (FAP) that predisposes to carcinomas of the colo-rectum, stomach, duodenum, and thyroid. Recently somatic mutations in exon 15 of APC gene have been described in certain sporadic papillary thyroid carcinomas. The prognostic impact of these mutations remains unknown in such settings.

Last updated: 2017-08-24 22:00:52 UTC
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Tier 3
APC
Variants
APC E1317Q
APC codon(s) 1307 frameshift
Primary Sites
Lung
Tumor Types
Squamous Cell Carcinoma
Adenocarcinoma
Interpretation

APC mutations have been reported in lung squamous cell carcinoma and small-cell lung carcinoma, but rarely in lung adenocarcinoma. However, variants in the APC gene have not been well characterized in lung adenocarcinoma and their clinical significance is unclear. According to ClinVar, this particular variant is a likely benign germline variant (https://preview.ncbi.nlm.nih.gov/clinvar/variation/829/).

Last updated: 2019-02-22 18:05:35 UTC
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Tier 3
APC
Variants
Primary Sites
Brain
Tumor Types
Glioblastoma
Interpretation

The APC gene encodes a tumor suppressor protein that acts as an antagonist of the Wnt signaling pathway. APC promotes rapid degradation of beta-catenin and participates in Wnt signaling as a negative regulator. APC is also involved in other processes including cell migration, cell adhesion, transcriptional activation and apoptosis. Germline defects in this gene cause familial adenomatous polyposis (FAP), an autosomal dominant pre-malignant disease that usually progresses to malignancy. Disease-associated mutations tend to be clustered in a small region designated the mutation cluster region (MCR) and result in a truncated protein product. Somatic mutations in this gene may be observed in colorectal cancer (CRC), stomach cancer and desmoid tumors. Although APC mutations have been reported in up to 5% of low grade gliomas and up to 13% primary glioblastomas (GBM), evidence regarding their involvement in CNS tumors is still limited. Further studies are needed to explore the clinical value of these mutations in CNS tumors.

Last updated: 2016-02-11 22:36:11 UTC
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Tier 3
APC
Variants
Primary Sites
Prostate
Tumor Types
Adenocarcinoma
Interpretation

The APC gene encodes a tumor suppressor protein that acts as an antagonist of the Wnt signaling pathway. APC promotes rapid degradation of beta-catenin and participates in Wnt signaling as a negative regulator. APC is also involved in other processes including cell migration, cell adhesion, transcriptional activation and apoptosis. Disease-associated mutations tend to be clustered in a small region designated the mutation cluster region (MCR) and result in a truncated protein product. APC mutations have been reported in 3-10% of prostate cancers. In some studies, a high-level of APC promoter methylation was shown to be an independent predictor of a poor prognosis in prostate cancers. However, further studies are needed to explore the clinical value of APC mutations in these tumors.

Last updated: 2016-04-17 17:40:57 UTC
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Tier 3
APC
Variants
APC I1307K
Primary Sites
Pancreas
Tumor Types
Adenocarcinoma
Interpretation

The APC gene encodes a tumor suppressor protein that acts as an antagonist of the Wnt signaling pathway. APC promotes rapid degradation of beta-catenin and participates in Wnt signaling as a negative regulator. APC is also involved in other processes including cell migration, cell adhesion, transcriptional activation and apoptosis. Germline defects in this gene cause familial adenomatous polyposis (FAP), an autosomal dominant pre-malignant disease that usually progresses to malignancy. Disease-associated mutations tend to be clustered in a small region designated the mutation cluster region (MCR) and result in a truncated protein product. Pancreatic cancer is considered a low risk cancer, though it is observed in FAP families with higher incidence than the general populations. Somatic APC mutations have been reported in ~1% of pancreatic ductal adenocarcinomas (PDAC). Codon I1307 lies within a regulatory region of the APC protein mediated by ubiquitination. APC I1307K is associated with increased colorectal cancer risk by making the gene unstable and prone to acquire mutations during normal cell division. The germline APC I1307K gene mutation is most commonly found in people of Ashkenazi Jewish descent. Therefore, routine colorectal screening is very important in these individuals. The prognostic and therapeutic implications of APC mutations in PDAC remain to be fully elucidated. Correlation with other clinical and lab findings is recommended.

Last updated: 2017-01-30 21:57:13 UTC
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Tier 3
APC
Variants
Primary Sites
Ovary
Tumor Types
Interpretation

The APC gene encodes a tumor suppressor protein that acts as an antagonist of the Wnt signaling pathway. APC promotes rapid degradation of beta-catenin and participates in Wnt signaling as a negative regulator. APC is also involved in other processes including cell migration, cell adhesion, transcriptional activation and apoptosis. Germline defects in this gene cause familial adenomatous polyposis (FAP), an autosomal dominant pre-malignant disease that usually progresses to malignancy. Disease-associated mutations tend to be clustered in a small region designated the mutation cluster region (MCR) and result in a truncated protein product. Somatic mutations in this gene may be observed in colorectal cancer (CRC), stomach cancer and desmoid tumors. Although APC mutations have been reported in ~2% of ovarian serous adenocarcinomas, further studies are needed to explore the clinical value of these mutations in ovarian cancers. Results should be interpreted in conjunction with other laboratory and clinical findings.

Last updated: 2017-02-06 20:00:54 UTC
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Tier 2
APC
Variants
APC any missense
APC any nonsense
APC any frameshift
Primary Sites
Small Intestine
Tumor Types
Adenocarcinoma
Interpretation

The APC gene encodes a tumor suppressor protein that acts as an antagonist of the Wnt signaling pathway. APC promotes rapid degradation of beta-catenin and participates in Wnt signaling as a negative regulator. APC is also involved in other processes including cell migration, cell adhesion, transcriptional activation and apoptosis. Germline defects in this gene cause familial adenomatous polyposis (FAP), an autosomal dominant pre-malignant disease that usually progresses to malignancy. Disease-associated mutations tend to be clustered in a small region designated as the mutation cluster region (MCR) and result in a truncated protein product. Somatic APC mutations are rare in adenocarcinoma of small intestine and further studies are needed to explore the clinical value of these mutations. Results should be interpreted in conjunction with other laboratory and clinical findings.

Last updated: 2017-04-17 23:08:15 UTC
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Tier 2
APC
Variants
APC copy number gain
APC 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 15:39:08 UTC
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Tier 2
APC
Variants
APC 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 15:40:02 UTC
Read More
Tier 2
APC
Variants
APC any missense
APC any nonsense
APC any frameshift
Primary Sites
Stomach
Tumor Types
Adenocarcinoma
Interpretation

The APC gene encodes a tumor suppressor protein that acts as an antagonist of the Wnt signaling pathway. APC promotes rapid degradation of beta-catenin and participates in Wnt signaling as a negative regulator. APC is also involved in other processes including cell migration, cell adhesion, transcriptional activation and apoptosis. Germline defects in this gene cause familial adenomatous polyposis (FAP), an autosomal dominant pre-malignant disease that usually progresses to malignancy. Disease-associated mutations tend to be clustered in a small region designated as the mutation cluster region (MCR) and result in a truncated protein product. A study of APC gene mutations in gastric carcinomas did not find an obvious relationship between the APC mutation and tumor size, depth of invasion, node metastasis or clinical stages, indicating a limited role of the APC mutation in predicting prognosis of gastric carcinomas. APC mutations were significantly more frequent in intestinal type gastric cancers as compared with diffuse type gastric cancers, suggesting that APC gene is not only a predisposing gene in colorectal cancer but also a predisposing gene in intestinal type of gastric cancer.

Last updated: 2018-03-06 18:02:46 UTC
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Tier 3
APC
Variants
APC I1307K
Primary Sites
Thyroid
Tumor Types
Papillary Carcinoma
Follicular Carcinoma
Interpretation

The APC gene encodes a tumor suppressor protein that acts as an antagonist of the Wnt signaling pathway. APC promotes rapid degradation of beta-catenin and participates in Wnt signaling as a negative regulator. APC is also involved in other processes including cell migration, cell adhesion, transcriptional activation and apoptosis. Germline defects in this gene cause familial adenomatous polyposis (FAP), an autosomal dominant pre-malignant disease that usually progresses to malignancy. Disease-associated mutations tend to be clustered in a small region designated the mutation cluster region (MCR) and result in a truncated protein product. Codon I1307 lies within a regulatory region of the APC protein mediated by ubiquitination. Germline APC I1307K is associated with increased colorectal cancer risk by making the gene unstable and prone to acquire mutations during normal cell division. The germline APC I1307K gene mutation is most commonly found in people of Ashkenazi Jewish descent. Therefore, routine colorectal screening is very important in these individuals. APC somatic mutations are found in less than 1% of thyroid carcinomas. The I1307K has not been reported as a somatic mutation in thyroid carcinoma to date. The prognostic and therapeutic implications of somatic APC mutations in thyroid carcinoma remain to be fully elucidated. Correlation with other clinical and lab findings is recommended.

Last updated: 2018-03-06 18:03:01 UTC
Read More
Tier 3
APC
Variants
APC I1307K
Primary Sites
Kidney
Tumor Types
Renal Cell Carcinoma
Clear Cell Renal Cell Carcinoma
Interpretation

The APC gene encodes a tumor suppressor protein that acts as an antagonist of the Wnt signaling pathway. APC promotes rapid degradation of beta-catenin and participates in Wnt signaling as a negative regulator. APC is also involved in other processes including cell migration, cell adhesion, transcriptional activation and apoptosis. Germline defects in this gene cause familial adenomatous polyposis (FAP), an autosomal dominant pre-malignant disease that usually progresses to malignancy. Disease-associated mutations tend to be clustered in a small region designated the mutation cluster region (MCR) and result in a truncated protein product. There is a case report of renal cell carcinoma occurring in a patient with attenuated FAP and a heterozygous germline APC deletion. Somatic APC mutations have been reported in ~1% of clear cell renal cell carcinomas. Codon I1307 lies within a regulatory region of the APC protein mediated by ubiquitination. APC I1307K is associated with increased colorectal cancer risk by making the gene unstable and prone to acquire mutations during normal cell division. The germline APC I1307K gene mutation is most commonly found in people of Ashkenazi Jewish descent. Therefore, routine colorectal screening is very important in these individuals. The prognostic and therapeutic implications of APC mutations in renal cell carcinoma remain to be fully elucidated. Correlation with other clinical and lab findings is recommended.

Last updated: 2018-03-06 18:03:24 UTC
Read More
Tier 3
APC
Variants
APC K1454E
Primary Sites
Breast
Tumor Types
Invasive Ductal Carcinoma
Lobular Carcinoma
Interpretation

The APC gene encodes a tumor suppressor protein that acts as an antagonist of the Wnt signaling pathway. APC promotes rapid degradation of beta-catenin and participates in Wnt signaling as a negative regulator. APC is also involved in other processes including cell migration, cell adhesion, transcriptional activation and apoptosis. Germline defects in this gene cause familial adenomatous polyposis (FAP), an autosomal dominant pre-malignant disease that usually progresses to malignancy. Somatic mutations in APC have been reported in around 2% of breast carcinomas. One study found that APC mutations in up to 18% of their breast cancer cohort and at a significantly high frequency in advanced stages of primary breast cancers. The APC K1454E variant has not been previously reported in breast carcinoma. The significance of this variant should be interpreted within the clinical context.

Last updated: 2018-03-06 18:03:54 UTC
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Tier 2
APC
Variants
APC I1307K
Primary Sites
Colon
Rectum
Tumor Types
Adenocarcinoma
Interpretation

Somatic APC mutations are common events in colorectal adenocarcinomas, reported in up to 76% of the cases. Loss of normal APC function is known to be an early event in both familial and sporadic colon cancer pathogenesis, occurring at the pre-adenoma stage. APC mutations do not appear to significantly affect the prognosis of colorectal cancer patients. While there are a number of small molecule inhibitors in development that target the Wnt pathway, there is currently no matched targeted therapy available for colorectal cancer patients harboring an APC mutation. Germline defects in this gene cause familial adenomatous polyposis (FAP), an autosomal dominant pre-malignant disease that usually progresses to malignancy. Disease-associated mutations tend to be clustered in a small region designated the mutation cluster region (MCR) and result in a truncated protein product. Codon I1307 lies within a regulatory region of the APC protein mediated by ubiquitination. APC I1307K is associated with increased colorectal cancer risk by making the gene unstable and prone to acquire mutations during normal cell division. The germline APC I1307K gene mutation is most commonly found in people of Ashkenazi Jewish descent. Therefore, routine colorectal screening is very important in these individuals. Correlation with other clinical and lab findings is recommended.

Last updated: 2018-03-16 19:52:48 UTC
Read More
Tier 3
APC
Variants
APC I1307K
Primary Sites
Breast
Tumor Types
Invasive Ductal Carcinoma
Interpretation

The APC gene encodes a tumor suppressor protein that acts as an antagonist of the Wnt signaling pathway. APC promotes rapid degradation of beta-catenin and participates in Wnt signaling as a negative regulator. APC is also involved in other processes including cell migration, cell adhesion, transcriptional activation and apoptosis. Germline defects in this gene cause familial adenomatous polyposis (FAP), an autosomal dominant pre-malignant disease that usually progresses to malignancy. Disease-associated mutations tend to be clustered in a small region designated the mutation cluster region (MCR) and result in a truncated protein product. Somatic APC mutations have been reported in less than 1% of breast invasive ductal carcinoma. Codon I1307 lies within a regulatory region of the APC protein mediated by ubiquitination. Germline APC I1307K is associated with increased colorectal cancer risk by making the gene unstable and prone to acquire mutations during normal cell division. The germline APC I1307K gene mutation is most commonly found in people of Ashkenazi Jewish descent. Therefore, routine colorectal screening is very important in these individuals. The prognostic and therapeutic implications of APC mutations in breast carcinoma remain to be fully elucidated. Correlation with other clinical and lab findings is recommended

Last updated: 2018-03-30 16:08:34 UTC
Read More
Tier 3
APC
Variants
APC I1307K
Primary Sites
Lung
Tumor Types
Adenocarcinoma
Interpretation

The APC gene encodes a tumor suppressor protein that acts as an antagonist of the Wnt signaling pathway. APC promotes rapid degradation of beta-catenin and participates in Wnt signaling as a negative regulator. APC is also involved in other processes including cell migration, cell adhesion, transcriptional activation and apoptosis. Germline defects in this gene cause familial adenomatous polyposis (FAP), an autosomal dominant pre-malignant disease that usually progresses to malignancy. Disease-associated mutations tend to be clustered in a small region designated the mutation cluster region (MCR) and result in a truncated protein product. Codon I1307 lies within a regulatory region of the APC protein mediated by ubiquitination. Germline APC I1307K is associated with increased colorectal cancer risk by making the gene unstable and prone to acquire mutations during normal cell division. The germline APC I1307K gene mutation is most commonly found in people of Ashkenazi Jewish descent. Therefore, routine colorectal screening is very important in these individuals. One study showed that males had significantly increased I1307K carrier prevalence in lung, urologic, pancreatic, and skin cancers. APC somatic mutations are found 4% of lung adenocarcinomas. The I1307K has not been reported as a somatic mutation in lung adenocarcinomas to date. The prognostic and therapeutic implications of somatic APC mutations in lung adenocarcinomas remain to be fully elucidated. Correlation with other clinical and lab findings is recommended.

Last updated: 2019-01-22 19:24:45 UTC
Read More
Tier 3
APC
Variants
APC K1454E
Primary Sites
Lung
Tumor Types
Adenocarcinoma
Interpretation

The APC gene encodes a tumor suppressor protein that acts as an antagonist of the Wnt signaling pathway. APC promotes rapid degradation of beta-catenin and participates in Wnt signaling as a negative regulator. Germline defects in this gene cause familial adenomatous polyposis (FAP), an autosomal dominant pre-malignant disease that usually progresses to malignancy. Somatic mutations in APC have been reported in 4% of lung adenocarcinomas, the prognostic and therapeutic implications of which remain to be fully elucidated. APC K1454E lies within the beta-catenin binding and down-regulation region of the Apc protein. K1454E suppresses beta-catenin mediated transcription at a level similar to wild-type Apc in a cell culture assay and therefore, is predicted to have no effect on Apc protein function. This variant has also been reported as a germline variant in prior studies and reported in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/RCV000200964/) as likely benign.

Last updated: 2019-08-29 17:55:08 UTC
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When using PMKB, please cite: Huang et al., JAMIA 2017


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