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SMAD4
Variants
VariantGeneTypeCOSMIC IDDNA Change (Coding Nucleotide)Exon
SMAD4 C324YSMAD4missenseCOSM14189971G>A9
SMAD4 R361HSMAD4missenseCOSM141221082G>A9
SMAD4 copy number gainSMAD4CNV
SMAD4 copy number lossSMAD4CNV
SMAD4 any mutationSMAD4any
SMAD4 I525VSMAD4missense12
SMAD4 any nonsenseSMAD4nonsense
SMAD4 R361CSMAD4missense9
SMAD4 P472TSMAD4missenseCOSM166704911
SMAD4 D351GSMAD4missense9
SMAD4 P356LSMAD4missenseCOSM140499

Interpretations

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Tier 3
SMAD4
Variants
Primary Sites
Colon
Rectum
Tumor Types
Adenocarcinoma
Interpretation

Colorectal cancers (CRCs) frequently harbor somatic mutations in the pathway members  SMAD4. The prevalence of SMAD4, SMAD2, and SMAD3 mutations in sporadic CRCs was 8.6% (64 of 744), 3.4% (25 of 744), and 4.3% (32 of 744), respectively. Somatic SMAD4 mutations have been reported to be more common in advanced stages of CRCs and LOH at the SMAD4 locus has been associated with poor prognosis. SMAD4 mutations were associated with mucinous histology.

Last updated: 2015-12-09 21:27:16 UTC
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Tier 2
SMAD4
Variants
SMAD4 any nonsense
Primary Sites
Pancreas
Tumor Types
Adenocarcinoma
Interpretation

SMAD4 is a tumor suppressor gene that is mutated in one third of colorectal cancer and half of pancreatic tumors. SMAD4 inactivation by allelic deletion or mutation mainly occurs in late stage pancreatic ductal adenocarcinoma and is associated with poorer prognosis. SMAD4 loss increased resistance to the chemotherapeutic agent 5'-fluorouracil.

Last updated: 2018-04-25 15:22:12 UTC
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Tier 3
SMAD4
Variants
Primary Sites
Lung
Tumor Types
Adenocarcinoma
Interpretation

Homozygous mutations causing SMAD4 loss are found in approximately 3% of lung adenocarcinomas and squamous cell carcinomas cases. SMAD4 loss tends to act synergistically with TP53 and KRAS mutations to increase lymphatic metastasis and tumor size. Experimental work in a mouse model has demonstrated increased susceptibility to DNA topoisomerase inhibitors with homozygous SMAD4 loss of function mutation coupled with KRAS G12D activating mutations.

Last updated: 2016-04-21 21:05:22 UTC
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Tier 3
SMAD4
Variants
SMAD4 C324Y
Primary Sites
Thyroid
Tumor Types
Papillary Carcinoma
Follicular Carcinoma
Interpretation

Smad4 is tumor suppressor gene and is crucial for thyroid development and function. It is key component of the transforming growth factor beta (TGFB) pathway which regulates the expression of thyroid-specific genes. The role of SMAD4 in thyroid tumorigenesis remains unclear. However, mutations affecting the coding region of the SMAD4 gene have been detected in some sporadic thyroid neoplasms. Studies that analyzed expression of SMAD4 in thyroid tumors gave contradictory results. Some studies showed that the expression of SMAD4 was reduced in thyroid cancer cells. Other studies indicated that it was expressed and present in the nucleus in all thyroid cell lines and controls analyzed, indicating propagation of TGFB signaling in thyroid tumors. Of note, a SMAD4 mutation C324Y, recently isolated from nodal metastases of papillary thyroid carcinoma (PTC), was confirmed to cause an increase in TGFB signaling and lead to the acquisition of transformed phenotype and invasive behavior in thyroid cells, enabling them to proliferate independently from thyroid-stimulating hormone.

Last updated: 2016-03-09 16:00:04 UTC
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Tier 3
SMAD4
Variants
Primary Sites
Breast
Tumor Types
Adenocarcinoma
Interpretation

SMAD4 is tumor suppressor gene and it encodes an intracellular mediator in the transforming growth factor β (TGF β) signal transduction pathway. Somatic mutations affecting the SMAD4 gene are rare in breast neoplasms and their role in breast tumorigenesis remains unclear. However, it has been demonstrated that SMAD4 protein expression is markedly downregulated or lost in breast ductal carcinoma when compared with that in the normal breast epithelium. Loss of SMAD4 protein expression may play a role in disease progression and overall prognosis in breast cancer patients but this need to be fully elucidated.

Last updated: 2016-06-01 13:53:34 UTC
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Tier 3
SMAD4
Variants
SMAD4 R361H
Primary Sites
Stomach
Tumor Types
Adenocarcinoma
Carcinoma
Interpretation

SMAD4 is a tumor suppressor gene and it encodes an intracellular mediator in the transforming growth factor β (TGF β) signal transduction pathway. The gene is inactivated in 40% of human gastric cancers by loss of heterozygosity, promoter hypermethylation, and somatic mutation. Prior sequencing studies have shown that SMAD4 is mutated in up to 8% of gastric cancers. SMAD4 p.R361H mutation occurs within the MH2 domain which is the SMAD-SMAD interaction and transcription activation domain of the protein. The loss of SMAD4, especially loss of nuclear SMAD4 expression, is involved in gastric cancer progression. Mutations at codon 361 have been previously reported in various tumor types. The exact clinical significance of this mutation in gastric cancers needs to be fully elucidated.

Last updated: 2016-10-11 21:49:56 UTC
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Tier 3
SMAD4
Variants
Primary Sites
Cervix
Tumor Types
Adenocarcinoma
Squamous Cell Carcinoma
Interpretation

SMAD4 is a tumor suppressor gene encoding an intracellular mediator in the transforming growth factor β (TGF β) signal transduction pathway. SMAD4 mutations have been observed in ~3% of cervical cancers. Functional inactivation of SMAD4 was found in 4 of 13 cervical squamous cancer cell lines, mostly due to homozygous loss. Loss of protein expression did not correlate with loss of heterozygosity and mutations in cervical squamous carcinomas; however, it was associated with poor disease-free and overall 5-year survival in one study. The predictive and prognostic significance of SMAD4 mutations in cervical cancers needs further elucidation. Results should be interpreted in conjunction with other laboratory and clinical findings.

Last updated: 2017-02-21 13:41:17 UTC
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Tier 3
SMAD4
Variants
Primary Sites
Bladder
Tumor Types
Urothelial Carcinoma
Interpretation

SMAD4 is a tumor suppressor gene encoding an intracellular mediator in the transforming growth factor β (TGF β) signal transduction pathway. SMAD4 mutations have been reported in up to 2% of urothelial carcinomas. The predictive and prognostic significance of SMAD4 mutations in urothelial carcinoma needs further elucidation. Results should be interpreted in conjunction with other laboratory and clinical findings.

Last updated: 2017-02-21 13:44:51 UTC
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Tier 2
SMAD4
Variants
SMAD4 copy number gain
SMAD4 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 15:39:51 UTC
Read More
Tier 2
SMAD4
Variants
SMAD4 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 15:40:47 UTC
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Tier 3
SMAD4
Variants
SMAD4 I525V
Primary Sites
Brain
Tumor Types
Astrocytoma, NOS
Astrocytoma, Anaplastic
Glioblastoma
Interpretation

SMAD4 is tumor suppressor gene and it encodes an intracellular mediator in the transforming growth factor b (TGF b) signal transduction pathway. Somatic mutations in SMAD4 are exceedingly rare in glial neoplasms. SMAD4 I525V has been reported as a likely benign germline variant in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/41788/). These results should be interpreted in the clinical context.

Last updated: 2018-03-21 18:17:15 UTC
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Tier 2
SMAD4
Variants
SMAD4 R361C
Primary Sites
Colon
Rectum
Tumor Types
Adenocarcinoma
Interpretation

Colorectal cancers (CRCs) frequently harbor somatic mutations in the pathway members SMAD4. The prevalence of SMAD4, SMAD2, and SMAD3 mutations in sporadic CRCs was 8.6% (64 of 744), 3.4% (25 of 744), and 4.3% (32 of 744), respectively. SMAD4 R361C lies at a hotspot residue within MH2 domain and has displayed reduced SMAD4 transactivating activity in cell assays. Somatic SMAD4 mutations have been reported to be more common in advanced stages of CRCs. Studies of loss of function somatic mutations and studies of loss of heterozygosity (LOH) at the SMAD4 locus have shown an association with poor prognosis. SMAD4 mutations were also associated with mucinous histology. There are ongoing clinical trials for colorectal tumors harboring SMAD4 alterations.

Last updated: 2018-05-02 20:04:30 UTC
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Tier 3
SMAD4
Variants
SMAD4 P472T
Primary Sites
Brain
Tumor Types
Glioblastoma
Interpretation

SMAD4 is a tumor suppressor gene and it encodes an intracellular mediator in the transforming growth factor b (TGF b) signal transduction pathway. SMAD4 mutations are very rare in glioblastoma and are present in less than 1% of cases and the significance of these mutations are unclear in this tumor type. The effect on protein function of SMAD4 P472T remains to be further elucidated. These results should be interpreted in the clinicopathologic context.

Last updated: 2018-06-13 18:55:27 UTC
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Tier 2
SMAD4
Variants
SMAD4 D351G
Primary Sites
Pancreas
Tumor Types
Adenocarcinoma
Interpretation

SMAD4 encodes a tumor suppressor and transcription factor that is a downstream effector in the TGF-ss signal transduction pathway. Germline mutations in SMAD4 have been associated with juvenile polyposis syndrome. SMAD4 is mutated in one third of colorectal cancer and half of pancreatic tumors. Genetic alterations in SMAD4 have been identified in 33% of pancreatic adenocarcinomas. SMAD4 inactivation by allelic deletion or mutation mainly occurs in late stage pancreatic ductal adenocarcinoma and is associated with poorer prognosis. SMAD4 D351G lies at a hotspot residue within the MH2 domain of the Smad4 protein (UniProt.org). D351G has been identified in sequencing studies, but has not been biochemically characterized and therefore, its effect on Smad4 protein function is unknown. The SMAD4 D351H variant has been described in human colorectal cancer cell lines and reported as likely oncogenic, suggesting that the D351G variant is also likely to be oncogenic. SMAD4 loss has been found to increase resistance to the chemotherapeutic agent 5'-fluorouracil.

Last updated: 2019-01-22 18:39:52 UTC
Read More
Tier 2
SMAD4
Variants
SMAD4 R361C
Primary Sites
Ampulla (Pancreaticobiliary Duct)
Tumor Types
Adenocarcinoma
Interpretation

SMAD4 encodes a tumor suppressor and transcription factor that is a downstream effector in the TGF-ss signal transduction pathway. Germline mutations in SMAD4 have been associated with juvenile polyposis syndrome (JPS). Loss of SMAD4 expression or somatic mutations in SMAD4 are found in pancreatic cancer and are associated with tumor grade. Somatic alterations in SMAD4 are observed at lower frequencies in multiple tumor types, including colon and lung adenocarcinoma. SMAD4 R361C lies at a hotspot residue within MH2 domain of the Smad4 protein (UniProt.org). R361C confers a loss of function to the Smad4 protein as demonstrated by reduced Smad4 transactivating activity in cell assays. The SMAD4 R361C mutation is likely oncogenic. Studies of loss of function somatic mutations and studies of loss of heterozygosity (LOH) at the SMAD4 locus have shown an association with poor prognosis. There are ongoing clinical trials for colorectal tumors harboring SMAD4 alterations.

Last updated: 2019-01-22 18:42:00 UTC
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Tier 2
SMAD4
Variants
SMAD4 any nonsense
Primary Sites
Small Intestine
Tumor Types
Adenocarcinoma
Interpretation

SMAD4 is a transcription factor that functions as a critical effector in the transforming growth factor beta (TGFss) signal pathway that controls cellular proliferation, differentiation and tissue homeostasis. The TGFss pathway suppresses tumorigenesis in premalignant states and promotes invasiveness and metastasis during cancer progression. Germline mutations in SMAD4 have been associated with juvenile polyposis syndrome (JPS). Somatic alterations in SMAD4 are in multiple tumor types, including colon and lung adenocarcinoma. SMAD4 inactivation by allelic deletion or mutation mainly occurs in late stage pancreatic ductal adenocarcinoma and is associated with poorer prognosis. SMAD4 loss increased resistance to the chemotherapeutic agent 5'-fluorouracil. The identified deletion is not characterized but is present at a site of frequent mutations and is potentially oncogenic. The role of SMAD4 variants in small intestinal adenocarcinomas need further characterization. Clinical correlation is recommended.

Last updated: 2019-01-22 18:42:56 UTC
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Tier 2
SMAD4
Variants
SMAD4 P356L
Primary Sites
Colon
Tumor Types
Adenocarcinoma
Interpretation

Colorectal cancers (CRCs) frequently harbor somatic mutations in the pathway members SMAD4. The prevalence of SMAD4, SMAD2, and SMAD3 mutations in sporadic CRCs was 8.6% (64 of 744), 3.4% (25 of 744), and 4.3% (32 of 744), respectively. Somatic SMAD4 mutations have been reported to be more common in advanced stages of CRCs and LOH at the SMAD4 locus has been associated with poor prognosis. SMAD4 mutations were associated with mucinous histology. SMAD4 P356L has been identified in tumors. Although it has not been biochemically characterized, it is a statistically significant hotspot and is predicted to be oncogenic.

Last updated: 2019-05-23 22:41:30 UTC
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Disclaimer: You assume full responsibility for all risks associated with using this PMKB website. The Englander Institute for Precision Medicine at Weill Cornell Medicine makes no guarantee of the comprehensiveness, reliability or accuracy of the information on this website and assumes no responsibility for errors in the information associated with this web site. Healthcare providers and patients must integrate all clinical and laboratory findings as well as information from a variety of sources before deciding on appropriate clinical care options.


When using PMKB, please cite: Huang et al., JAMIA 2017


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