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CDKN2A
Variants
VariantGeneTypeCOSMIC IDDNA Change (Coding Nucleotide)Exon
CDKN2A W110*CDKN2Anonsense2
CDKN2A Y129*CDKN2Anonsense2
CDKN2A copy number lossCDKN2ACNV
CDKN2A V126DCDKN2Amissense377T>A2
CDKN2A copy number gainCDKN2ACNV
CDKN2A any mutationCDKN2Aany
CDKN2A any frameshiftCDKN2Aframeshift
CDKN2A H83YCDKN2Amissense2
CDKN2A codon(s) 58 frameshiftCDKN2Aframeshift2
CDKN2A codon(s) 80 frameshiftCDKN2Aframeshift2
CDKN2A D108HCDKN2Amissense2
CDKN2A R128WCDKN2Amissense2
CDKN2A G67CCDKN2Amissense2
CDKN2A D84VCDKN2Amissense2

Interpretations

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Tier 2
CDKN2A
Variants
CDKN2A W110*
CDKN2A Y129*
CDKN2A any frameshift
CDKN2A H83Y
CDKN2A codon(s) 58 frameshift
CDKN2A codon(s) 80 frameshift
CDKN2A D108H
Primary Sites
Lung
Tumor Types
Squamous Cell Carcinoma
Interpretation

Somatic mutations of CDKN2A are present in various tumor types, including, squamous cell carcinoma of the lung, clear cell sarcoma, head and neck cancer, melanoma and esophageal cancer. Majority of the CDKN2A mutations span exon 2 and result in loss or decreased binding to CDK4/6 leading to uncontrolled cell growth through inactivation of Rb and p53 pathways. Multiple preclinical and clinical studies are ongoing for CDKN2A deficient tumors in multiple tumor types.

Last updated: 2018-06-13 19:01:26 UTC
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Tier 2
CDKN2A
Variants
CDKN2A W110*
CDKN2A any frameshift
Primary Sites
Skin
Tumor Types
Melanoma
Interpretation

Somatic mutations of CDKN2A are present in various tumor types, including, squamous cell carcinoma of the larynx, clear cell sarcoma, head and neck cancer, melanoma and esophageal cancer. Majority of the CDKN2A mutations span exon 2 and result in loss or decreased binding to CDK4/6 leading to uncontrolled cell growth through inactivation of Rb and p53 pathways. Multiple preclinical and clinical studies are ongoing for CDKN2A deficient tumors in multiple tumor types.

Last updated: 2018-10-11 19:06:59 UTC
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Tier 3
CDKN2A
Variants
CDKN2A W110*
Primary Sites
Esophagus
Tumor Types
Carcinoma
Interpretation

Somatic mutations of CDKN2A are present in various tumor types, including, squamous cell carcinoma of the larynx, clear cell sarcoma, head and neck cancer, melanoma and esophageal cancer. Majority of the CDKN2A mutations span exon 2 and result in loss or decreased binding to CDK4/6 leading to uncontrolled cell growth through inactivation of Rb and p53 pathways. Multiple preclinical and clinical studies are ongoing for CDKN2A deficient tumors in multiple tumor types.

Last updated: 2018-03-06 17:55:09 UTC
Read More
Tier 2
CDKN2A
Variants
CDKN2A Y129*
CDKN2A W110*
CDKN2A any frameshift
CDKN2A codon(s) 58 frameshift
CDKN2A codon(s) 80 frameshift
Primary Sites
Lung
Tumor Types
Adenocarcinoma
Interpretation

Somatic mutations of CDKN2A are present in various tumor types, including, squamous cell carcinoma of the larynx, clear cell sarcoma, head and neck cancer, melanoma and esophageal cancer, among other cancer types. Majority of the CDKN2A mutations span exon 2 and result in loss or decreased binding to CDK4/6 leading to uncontrolled cell growth through inactivation of Rb and p53 pathways. Multiple preclinical and clinical studies are ongoing for CDKN2A deficient tumors in multiple tumor types.

Last updated: 2018-04-19 15:53:50 UTC
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Tier 2
CDKN2A
Variants
Primary Sites
Colon
Rectum
Tumor Types
Adenocarcinoma
Squamous Cell Carcinoma
Interpretation

CDKN2A gene functions as an important tumour suppressor in various human malignancies including colorectal cancer, and its activation prevents carcinogenesis via induction of cell growth arrest and senescence. Majority of the CDKN2A mutations span exon 2 and result in loss or decreased binding to CDK4/6 leading to uncontrolled cell growth through inactivation of Rb and p53 pathways. Somatic mutations of CDKN2A are present in various tumor types but have not been well characterized in colorectal cancer. However, epigenetic silencing of CDKN2A by hypermethylation has been reported be a possible predictive factor of poor prognosis in patients with colorectal cancer.

Last updated: 2016-11-04 00:48:03 UTC
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Tier 2
CDKN2A
Variants
CDKN2A copy number loss
Primary Sites
Brain
Tumor Types
Glioblastoma
Interpretation

The CDKN2A gene locus is altered in up to approximately 57% of glioblastoma, most commonly as a homozygous deletion, and frequently with concurrent deletion of the CDKN2B locus. CDKN2A/CDKN2B loss may be associated with increased sensitivity to CDK4/6 inhibitors. The efficacy and toxicity profiles of these inhibitors in the context of a variety of cancer types are currently under evaluation in clinical trials.

Last updated: 2019-04-26 15:04:50 UTC
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Tier 2
CDKN2A
Variants
Primary Sites
Liver
Ampulla (Pancreaticobiliary Duct)
Tumor Types
Cholangiocarcinoma
Adenocarcinoma
Interpretation

CDKN2A gene functions as an important tumor suppressor in various human malignancies including cholangiocarcinomas, and its activation prevents carcinogenesis via induction of cell growth arrest and senescence. Majority of the CDKN2A mutations span exon 2 and result in loss or decreased binding to CDK4/6 leading to uncontrolled cell growth through inactivation of Rb and p53 pathways. Somatic mutations of CDKN2A are present in various tumor types including cholangiocarcinomas where they appear to be more common in extrahepatic cholangiocarcinomas (up to 15%) than in intrahepatic ones. However, epigenetic silencing of CDKN2A by hypermethylation is more frequent, and the frequency ranges from 17% to 83% in different studies. Of note, inactivation of CDKN2A may portend poor clinical outcome according to some studies. However, correlation with other clinical and lab findings is necessary.

Last updated: 2016-11-04 00:47:49 UTC
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Tier 3
CDKN2A
Variants
CDKN2A copy number loss
Primary Sites
Thyroid
Tumor Types
Papillary Carcinoma
Follicular Carcinoma
Interpretation

CDKN2A gene encodes p16 and functions as an important tumor suppressor in various human malignancies. Its activation prevents carcinogenesis via induction of cell growth arrest and senescence. Majority of the CDKN2A mutations span exon 2 and result in loss or decreased binding to CDK4/6 leading to uncontrolled cell growth through inactivation of Rb and p53 pathways. Genetic alterations (deletion, mutation, and methylation) in p16 associated with loss of function have been reported in cell lines and primary thyroid tumors. However, predictive or prognostic significance of p16 in thyroid cancer is not clear and correlation with other clinical and lab findings is necessary. Multiple clinical trials are available for patients with CDKN2A deficient tumors.

Last updated: 2016-08-12 21:53:06 UTC
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Tier 2
CDKN2A
Variants
CDKN2A copy number loss
Primary Sites
Stomach
Tumor Types
Adenocarcinoma
Interpretation

CDKN2A generates several transcript variants including p16 and p14ARF. P16 regulates cell cycle by inhibiting CDK4 and CDK6, and thus preventing progression from G1 to S phase. P14ARF acts as a tumor suppressor by inhibiting ribosome biogenesis and initiating p53-dependent cell cycle arrest and apoptosis. Mutations and deletion of CDKN2A are reported in up to 34% of gastric cancer. In addition, EBV-positive gastric adenocarcinoma showed CDKN2A promoter hypermethylation. Gastric cancer with CDKN2A mutations has been shown to be sensitive to CDK4/6 inhibitors in vitro studies. However, predictive or prognostic significance of CDKN2A mutation in gastric cancer is not clear and correlation with other clinical and laboratory findings is necessary. Multiple clinical trials are available for patients with CDKN2A deficient tumors.

Last updated: 2020-07-24 14:53:03 UTC
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Tier 2
CDKN2A
Variants
CDKN2A copy number loss
Primary Sites
Skin
Tumor Types
Melanoma
Interpretation

CDKN2A gene functions as an important tumor suppressor via induction of cell growth arrest and senescence. Majority of the CDKN2A mutations result in loss or decreased binding to CDK4/6 leading to uncontrolled cell growth through inactivation of Rb and p53 pathways. CDKN2A is the major high-risk susceptibility gene identified in melanoma. Somatic mutations of CDKN2A are reported in up to 19% and 20% of cutaneous and desmoplastic melanoma, respectively. Germline mutations have been reported in ~20-40% of families with melanoma. Correlation with other clinical and lab findings is necessary.

Last updated: 2016-11-04 00:44:59 UTC
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Tier 2
CDKN2A
Variants
CDKN2A copy number loss
Primary Sites
Liver
Tumor Types
Hepatocellular Carcinoma
Interpretation

CDKN2A gene functions as an important tumor suppressor via induction of cell growth arrest and senescence. Majority of the CDKN2A mutations result in loss or decreased binding to CDK4/6 leading to uncontrolled cell growth through inactivation of Rb and p53 pathways. Somatic mutations of CDKN2A are present in various tumor types including ~2-3% of hepatocellular carcinoma (HCC). However, epigenetic silencing of CDKN2A by promoter hypermethylation is more frequent, occurring in 73% of HCC, 56% of HBV-related HCC, and 84% of HCV-related HCC. Clinical trials for CDKN2A deficient tumors are available. Correlation with other clinical and lab findings is necessary.

Last updated: 2016-11-04 00:46:32 UTC
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Tier 2
CDKN2A
Variants
CDKN2A copy number loss
Primary Sites
Pancreas
Tumor Types
Adenocarcinoma
Interpretation

CDKN2A gene encodes p16 and functions as an important tumor suppressor in various human malignancies. Its activation prevents carcinogenesis via induction of cell growth arrest and senescence. The majority of the CDKN2A mutations span exon 2 and result in loss or decreased binding to CDK4/6, leading to uncontrolled cell growth through inactivation of Rb and p53 pathways. Genetic alterations in CDKN2A have been reported in up to 41% of pancreatic adenocarcinomas (36% CNV loss and 5% SNV alterations). Few studies have suggested that CDKN2A is a causative gene in familial pancreatic cancer families. Germline mutations of CDKN2A among patients with pancreatic cancer are rare (<1%), with estimated penetrance of 58% and 39% for pancreatic cancer and melanoma, respectively. Multiple clinical trials are available for patients with CDKN2A deficient tumors. Predictive and prognostic significance of CDKN2A alterations in pancreatic cancer is not clear and correlation with other clinical and lab findings is necessary.

Last updated: 2017-03-02 23:18:55 UTC
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Tier 2
CDKN2A
Variants
CDKN2A V126D
Primary Sites
Skin
Tumor Types
Melanoma
Interpretation

CDKN2A gene functions as an important tumor suppressor via induction of cell growth arrest and senescence. Majority of the CDKN2A mutations result in loss or decreased binding to CDK4/6 leading to uncontrolled cell growth through inactivation of Rb and p53 pathways. CDKN2A is a major high-risk susceptibility gene identified in melanoma. Somatic mutations of CDKN2A are reported in up to 19% and 20% of cutaneous and desmoplastic melanomas, respectively. Germline mutations have been reported in ~20-40% of families with melanoma. CDKN2A V126D mutation has been reported in numerous cases of familial melanoma and shown to be a loss-of-function mutation with reduced CDK4 binding. Correlation with other clinical and lab findings is necessary.

Last updated: 2017-04-10 19:10:58 UTC
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Tier 2
CDKN2A
Variants
CDKN2A copy number gain
CDKN2A 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
Parathyroid
Penis
Peripheral Nervous System
Peritoneum
Pharynx
Pituitary
Placenta
Pleura
Prostate
Retroperitoneum
Salivary Gland
Seminal Vesicle
Skeletal Muscle
Skin
Small Intestine
Soft Tissue
Spleen
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 Lymphoma
Gastrointestinal Stromal Tumor
Germ Cell Tumor
Giant Cell Tumor
Glomus Tumor
Granular Cell Tumor
Hairy Cell Leukemia
Hemangioendothelioma
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
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 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: 2018-10-30 15:40:05 UTC
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Tier 2
CDKN2A
Variants
CDKN2A 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 15:40:09 UTC
Read More
Tier 2
CDKN2A
Variants
CDKN2A codon(s) 80 frameshift
Primary Sites
Esophagus
Tumor Types
Squamous Cell Carcinoma
Interpretation

CDKN2A gene functions as an important tumor suppressor via induction of cell growth arrest and senescence. Majority of the CDKN2A mutations result in loss or decreased binding to CDK4/6 leading to uncontrolled cell growth through inactivation of RB and p53 pathways. CDKN2A alterations have been reported as frequent mutations in squamous cell carcinomas of different primary sites including the lung, head and neck, and skin. CDKN2A R80* results in a premature truncation and confers a loss of function to the CDKN2A protein as demonstrated by loss of CDK binding. CDKN2A truncating mutations, including R80*, have been described in approximately 4% of esophageal squamous cell carcinomas. CDKN2A/CDKN2B loss may be associated with increased sensitivity to CDK4/6 inhibitors. The efficacy and toxicity profiles of these inhibitors in the context of a variety of cancer types are currently under evaluation in clinical trials. The clinical significance of the loss of one copy of CDKN2A remains to be fully elucidated in squamous cell carcinoma of the esophagus. These results should be interpreted in the clinicopathologic context.

Last updated: 2018-03-06 18:01:09 UTC
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Tier 2
CDKN2A
Variants
CDKN2A codon(s) 58 frameshift
Primary Sites
Bladder
Tumor Types
Squamous Cell Carcinoma
Interpretation

CDKN2A gene functions as an important tumor suppressor via induction of cell growth arrest and senescence. Majority of the CDKN2A mutations result in loss or decreased binding to CDK4/6 leading to uncontrolled cell growth through inactivation of RB and p53 pathways. CDKN2A alterations have been reported as frequent mutations in squamous cell carcinomas of different primary sites including the lung, head and neck, and skin. CDKN2A R58* results in a premature truncation and confers a loss of function to the CDKN2A protein as demonstrated by loss of CDK binding. CDKN2A/CDKN2B loss may be associated with increased sensitivity to CDK4/6 inhibitors. The efficacy and toxicity profiles of these inhibitors in the context of a variety of cancer types are currently under evaluation in clinical trials. The clinical significance of the loss of one copy of CDKN2A remains to be fully elucidated in squamous cell carcinoma of the bladder. These results should be interpreted in the clinicopathologic context.

Last updated: 2018-03-06 18:01:26 UTC
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Tier 2
CDKN2A
Variants
CDKN2A H83Y
Primary Sites
Brain
Brain, Infratentorial
Brain, Supratentorial
Tumor Types
Glioblastoma
Interpretation

CDKN2A H83Y lies within the ANK3 domain of the CDKN2A protein. H83Y confers a loss of function to the CDKN2A protein as demonstrated by loss of cell cycle control. The CDKN2A gene locus is altered in up to approximately 57% of glioblastoma, most commonly as a homozygous deletion, and frequently with concurrent deletion of the CDKN2B locus. CDKN2A/CDKN2B loss may be associated with increased sensitivity to CDK4/6 inhibitors. The efficacy and toxicity profiles of these inhibitors in the context of a variety of cancer types are currently under evaluation in clinical trials. CDKN2A mutations account for only 1-3% of glioblastomas and the clinical significance remains to be elucidated.

Last updated: 2018-03-06 18:01:48 UTC
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Tier 2
CDKN2A
Variants
CDKN2A any frameshift
Primary Sites
Gall Bladder
Tumor Types
Adenocarcinoma
Interpretation

CDKN2A gene encodes p16 and functions as an important tumor suppressor in various human malignancies. Its activation prevents carcinogenesis via induction of cell growth arrest and senescence. The majority of the CDKN2A mutations span exon 2 and result in loss or decreased binding to CDK4/6 leading to uncontrolled cell growth through inactivation of Rb and p53 pathways. CDKN2A alterations are common, occurring in 60-70% of gallbladder carcinomas, by mechanisms including point mutations, chromosomal loss, and promoter methylation. These somatic CDKN2A alterations are associated with a poor prognosis. A frameshift insertion at codon 57 in exon 2 will result in early truncation of the p16 protein. Multiple clinical trials are available for patients with CDKN2A deficient tumors.

Last updated: 2018-03-06 18:02:04 UTC
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Tier 2
CDKN2A
Variants
CDKN2A W110*
Primary Sites
Brain
Tumor Types
Glioblastoma
Astrocytoma, NOS
Astrocytoma, Anaplastic
Interpretation

The CDKN2A gene locus is altered in up to approximately 57% of glioblastoma, most commonly as a homozygous deletion, and frequently with concurrent deletion of the CDKN2B locus. CDKN2A/CDKN2B loss may be associated with increased sensitivity to CDK4/6 inhibitors. W110* results in early truncation and confers a loss of function as demonstrated by loss of CDK binding and cell cycle control in culture. The clinicopathologic effects of the heterozygous rather than homozygous loss of CDKN2A in glial neoplasms remains to be further elucidated. The efficacy and toxicity profiles of these inhibitors in the context of a variety of cancer types are currently under evaluation in clinical trials.

Last updated: 2018-03-30 16:06:22 UTC
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Tier 2
CDKN2A
Variants
CDKN2A R128W
Primary Sites
Colon
Tumor Types
Adenocarcinoma
Interpretation

CDKN2A gene functions as an important tumor suppressor in various human malignancies including colorectal cancer, and its activation prevents carcinogenesis via induction of cell growth arrest and senescence. Majority of the CDKN2A mutations span exon 2 and result in loss or decreased binding to CDK4/6 leading to uncontrolled cell growth through inactivation of Rb and p53 pathways. Somatic mutations of CDKN2A are present in various tumor types but have not been well characterized in colorectal cancer. However, epigenetic silencing of CDKN2A by hypermethylation has been reported to be a possible predictive factor of poor prognosis in patients with colorectal cancer. CDKN2A R128W is predicted to confer a loss of function to the CDKN2A protein, as demonstrated by a loss of Sp1 binding. CDKN2A R128Q has been shown to be associated with dysplasia in the setting of Barrett's esophagus. However, its prognostic and therapeutic significance in colorectal carcinomas remains to be fully elucidated.

Last updated: 2019-02-22 18:07:06 UTC
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Tier 2
CDKN2A
Variants
CDKN2A G67C
Primary Sites
Lung
Tumor Types
Adenocarcinoma
Interpretation

CDKN2A gene functions as an important tumour suppressor in various human malignancies and somatic mutations in this gene are present in various tumor types, including, lung adenocarcinoma, squamous cell carcinoma of the larynx, clear cell sarcoma, head and neck cancer, melanoma and esophageal cancer, among other cancer types. Majority of the CDKN2A mutations span exon 2 and result in loss or decreased binding to CDK4/6 leading to uncontrolled cell growth through inactivation of Rb and p53 pathways. This particular variant G67C is considered to be likely pathogenic based on the known pathogenicity of G67R/S. Multiple preclinical and clinical studies are ongoing for CDKN2A deficient tumors in multiple tumor types.

Last updated: 2019-07-15 15:40:29 UTC
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Tier 2
CDKN2A
Variants
CDKN2A codon(s) 58 frameshift
CDKN2A codon(s) 80 frameshift
Primary Sites
Skin
Unknown
Tumor Types
Melanoma
Interpretation

Somatic mutations of CDKN2A are present in various tumor types, including, squamous cell carcinoma of the larynx, clear cell sarcoma, head and neck cancer, esophageal cancer and melanoma. Germline aberrations in the CDKN2A gene are also observed in some melanoma-prone families, representing high penetrance mutations. Majority of the CDKN2A mutations span exon 2 and result in loss or decreased binding to CDK4/6 leading to uncontrolled cell growth through inactivation of Rb and p53 pathways. Multiple preclinical and clinical studies are ongoing for CDKN2A deficient tumors in multiple tumor types. Correlation with clinical findings and genetic counseling may be helpful if there is clinical concern for an inherited cancer syndrome.

Last updated: 2019-07-15 15:40:47 UTC
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Tier 2
CDKN2A
Variants
CDKN2A D84V
Primary Sites
Lung
Unknown
Skin
Tumor Types
Adenosarcoma
Squamous Cell Carcinoma
Melanoma
Interpretation

Somatic mutations of CDKN2A are present in various tumor types, including, squamous cell carcinoma of the lung, clear cell sarcoma, head and neck cancer, melanoma and esophageal cancer. Majority of the CDKN2A mutations span exon 2 and result in loss or decreased binding to CDK4/6 leading to uncontrolled cell growth through inactivation of Rb and p53 pathways. The D84V mutant is predicted to confer loss of function to the CDKN2A protein as demonstrated by an inability to bind and inhibit the cyclin-dependent kinases CDK4 and CDK6. Multiple preclinical and clinical studies are ongoing for CDKN2A deficient tumors in multiple tumor types.

Last updated: 2019-07-15 15:41:03 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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