Gene

CDKN2A

cyclin dependent kinase inhibitor 2A

Explore in graph →CI-GENE-00040778HGNC:1787 ENSG00000147889 NCBI 1029 CIViC Cancer geneApproved

Curated evidence

Clinical evidence (61)

CIViC items involving this gene, grouped by molecular profile and therapy, with native levels and directions. 50 items per page.

civicCuratedShowing 1–50 of 61 evidence items · levels, directions and significance as curated at the source; each row links to its CIViC record.

Therapy	Cancer	Type	Level	Direction · significance	Rating (1–5)	Status	Evidence	Source
AXIN2 P455K + BAX L76R + BRAF V600E + CDKN2A Deletion + CDKN2B Deletion + TET2 E796KCDKN2B TET2 BAX AXIN2 BRAF CDKN2A1

Cohorts

Alteration frequency by cohort (197)

Frequency = cases affected / cases profiled within one cohort. Cohorts are never pooled.

cbioportalObserved197 cohort rows (showing 50, sorted by frequency) · frequency = affected / profiled, as published by each cohort; cohorts are not pooled. Hover a row badge for its release.

Cohort	Mapped cancer	Alteration	Affected (n)	Profiled (n)	Frequency (%)	Rank in cohort	Source
Metastatic Esophagogastric Cancer (MSK, Cancer Discovery 2017) egc_msk_2017	Gastroesophageal Junction Adenocarcinoma	Ssm

Literature

Linked publications (24)

25 per page, newest first.

pubmedPublishedShowing 1–24 of 24 publications · bibliographic data as recorded by PubMed; abstracts are not reproduced.

Human papillomavirus and survival of patients with oropharyngeal cancer.
· N Engl J Med · 2010 · PMID 20530316 · validated civic_curation pubmed
Prognostic significance of human papillomavirus in recurrent or metastatic head and neck cancer: an analysis of Eastern Cooperative Oncology Group trials.
· Ann Oncol · 2014 · PMID 24799460 · validated civic_curation pubmed
Impact of human papilloma virus infection on the response of head and neck cancers to anti-epidermal growth factor receptor antibody therapy.
· Cell Death Dis · 2014 · PMID 24577089 · validated civic_curation pubmed
Association of Human Papillomavirus and p16 Status With Outcomes in the IMCL-9815 Phase III Registration Trial for Patients With Locoregionally Advanced Oropharyngeal Squamous Cell Carcinoma of the Head and Neck Treated With Radiotherapy With or Without Cetuximab.

CDKN2A A20P2
(functional)	—UNRESOLVED	Functional	D	Supports Loss Of Function	3	submitted	EID9323 Analysis of several CDKN2A variants was performed to discover their functional impact. Both in vitro and in vivo binding assays showed that the A20P mutation resulted in complete loss of binding to CD… (full text at CIViC) PMID 10498896 · Ruas et al., 1999 · Open in CIViC	civic
Palbociclib	Melanoma	Predictive	D	Supports Sensitivity Response	—	submitted	EID4524 In an in vitro study, a melanoma C052 cell line expressing CDKN2A A20P mutation (endogenous) demonstrated sensitivity to palbociclib treatment (GI50: 79nM). Sensitivity was determined by assessing cel… (full text at CIViC) PMID 24495407 · Young et al., 2014 · Open in CIViC	civic

CDKN2A Deletion3
(prognostic)	Childhood Low Grade Glioma	Prognostic	B	Supports Poor Outcome	4	accepted	EID7192 CDKN2A deletion was identified in 24 of 273 patients with PLGGs using FISH analysis. An association between this alteration and BRAFV600E was detected (p=0.0001). Hemispheric tumors with CDKN2A deleti… (full text at CIViC) PMID 29948154 · Yang et al., 2018 · Open in CIViC	civic
〃	Acute Lymphoblastic Leukemia	Prognostic	B	Supports Poor Outcome	4	rejected	EID7985 CDKN2A/B deletions were poor prognostic factors for both overall survival (OS) (HR = 2.15, 95% CI 1.82-2.54) and event-free survival (EFS)/disease-free survival (DFS)/relapse-free survival (RFS) (HR =… (full text at CIViC) PMID 30592434 · Zhang et al., 2019 · Open in CIViC	civic
Palbociclib	Gastrointestinal Stromal Tumor	Predictive	B	Does Not Support Sensitivity Response	4	submitted	EID7311 In a phase 2 trial, patients with GIST bearing CDKN2A gene loss were treated with Palbociclib. 86.4% of patients had PD at 4 months. PMID 30979737 · Toulmonde et al., 2019 · Open in CIViC	civic

CDKN2A L16P2
(functional)	—UNRESOLVED	Functional	D	Supports Loss Of Function	3	submitted	EID9321 Analysis of several CDKN2A variants was performed to discover their functional impact. An in vitro binding assay found that CDKN2A L16P resulted in decreased binding to CDK4 and CDK6. Protein structur… (full text at CIViC) PMID 10498896 · Ruas et al., 1999 · Open in CIViC	civic
〃	—UNRESOLVED	Functional	D	Supports Loss Of Function	3	rejected	EID9322 Analysis of several CDKN2A variants was performed to discover their functional impact. An in vitro binding assay found that CDKN2A L16P resulted in decreased binding to CDK4 and CDK6. Protein structur… (full text at CIViC) PMID 10498896 · Ruas et al., 1999 · Open in CIViC	civic

CDKN2A Loss12
(prognostic)	Acute Lymphoblastic Leukemia	Prognostic	B	Supports Poor Outcome	4	accepted	EID7986 A total of thirteen studies including 2857 patients were combined in a meta-analysis. Combined HRs suggested that CDKN2A/B deletions were poor prognostic factors for both overall survival (OS) (HR = 2… (full text at CIViC) PMID 30592434 · Zhang et al., 2019 · Open in CIViC	civic
Alvocidib	Cutaneous MelanomaALIAS	Predictive	D	Supports Sensitivity Response	2	accepted	EID1372 Preclinical study in 9 melanoma cell lines. Three cell lines did not have CDKN2A (p16) mutations and showed expression of the protein on western blot analysis. Two of the other six cell lines had stop… (full text at CIViC) PMID 12777976 · Robinson et al., 2003 · Open in CIViC	civic
Immune Checkpoint Inhibitor	Bladder Urothelial Carcinoma	Predictive	B	Supports Resistance	3	accepted	EID12546 In retrospective analyses of two large ICI-treated solid tumor cohorts (DFCI n = 789, MSKCC n = 1250), CDKN2A loss-of-function alterations were associated with significantly worse overall survival and… (full text at CIViC) PMID 34074656 · Adib et al., 2021 · Open in CIViC	civic
Letrozole + PalbociclibCombination	HER2 Negative Breast CancerUNRESOLVED	Predictive	C	Supports Sensitivity Response	3	accepted	EID1765 A patient with metastatic ER-positive, her2-negative breast cancer with CDKN2A loss experienced a short-lived (~3-month) clinical response to palbociclib when given in combination with letrozole. PMID 26715889 · Gao et al., 2015 · Open in CIViC	civic
Palbociclib	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	B	Does Not Support Resistance	2	accepted	EID7444 TAPUR, a phase II basket trial, included a cohort of patients with advanced non-small lung cell carcinoma (NSCLC) harboring with CDKN2A loss or mutation and no RB mutations. Twenty-nine patients were … (full text at CIViC) Open in CIViC	civic
〃	Renal Cell CarcinomaCURATED_BROADER	Predictive	D	Supports Sensitivity Response	3	accepted	EID1373 Preclinical study of CDK4/6 inhibitor PD-0332991 in 28 renal carcinoma cell lines (25 malignant RCC and three non-malignant, transformed cell lines derived from kidney epithelium). Both p15 and p16 lo… (full text at CIViC) PMID 23898052 · Logan et al., 2013 · Open in CIViC	civic
〃	Cutaneous MelanomaALIAS	Predictive	D	Supports Sensitivity Response	3	accepted	EID1375 In a cohort of 143 patients with primary invasive melanoma hemizygous or homozygous loss of CDKN2A was observed (FISH) in 56% of cases. PD0332991 efficacy (proliferation assay) was assessed in a panel… (full text at CIViC) PMID 24495407 · Young et al., 2014 · Open in CIViC	civic
〃	Malignant Ovarian Neoplasm	Predictive	D	Supports Sensitivity Response	3	accepted	EID1377 Preclinical study of the effects of PD-0332991 on proliferation, cell-cycle, apoptosis, and Rb phosphorylation in a panel of 40 human ovarian cancer cell lines. Concentration-dependent antiproliferati… (full text at CIViC) PMID 21278246 · Konecny et al., 2011 · Open in CIViC	civic
〃	GlioblastomaCURATED_BROADER	Predictive	D	Supports Sensitivity Response	2	submitted	EID1559 Short term explant cultures from 20 glioblastoma multiforme (GBM) tumor xenograft lines were evaluated for CDKN2A (p16 aka INK4A) expression by western blot and RT-PCR as well as deletion by aCGH and … (full text at CIViC) PMID 22711607 · Cen et al., 2012 · Open in CIViC	civic
〃	Dermatofibrosarcoma Protuberans	Predictive	D	Supports Sensitivity Response	2	accepted	EID1881 An imatinib-resistant cell line, DFSP105, was established from a dermatofibrosarcoma protuberans which had progressed to a high-grade fibrosarcomatous DFSP. The disease-associated COL1A1-PDGFB fusion … (full text at CIViC) PMID 25852058 · Eilers et al., 2015 · Open in CIViC	civic
Linsitinib + PalbociclibSubstitutes	Ewing Sarcoma	Predictive	D	Supports Sensitivity Response	2	accepted	EID1879 A patient-derived xenograft (PDX) from a patient with cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B) loss and FUS-ERG fusion positive Ewing's sarcoma was created. The PDX was treated in four cohort… (full text at CIViC) PMID 27286459 · Murakami et al., 2016 · Open in CIViC	civic
Dabrafenib + VemurafenibSubstitutes	Melanoma	Predictive	B	Supports Resistance	4	submitted	EID7679 In a retrospective study, authors analyzed 100 tumor samples from 44 patients with BRAF mutant melanoma whose tumor developed acquired resistance to either vemurafenib or dabrafenib monotherapy. Among… (full text at CIViC) PMID 24265155 · Shi et al., 2014 · Open in CIViC	civic

CDKN2A Loss + CDKN2A Mutation2
Palbociclib	Malignant Pancreatic Neoplasm	Predictive	B	Does Not Support Sensitivity Response	3	accepted	EID11653 A phase II clinical study conducted with 12 patients with pancreatic cancer with CDKN2A loss or mutation treated with palbociclib. No clinical activity demonstrated in patients with CDKN2A mutated/del… (full text at CIViC) PMID 35100714 · Al Baghdadi et al., 2019 · Open in CIViC	civic
〃	Malignant Biliary Tract NeoplasmALIAS	Predictive	B	Does Not Support Sensitivity Response	3	accepted	EID11654 A phase II clinical study conducted in 10 patients with biliary cancer with CDKN2A loss or mutation, that were treated with palbociclib. No clinical activity demonstrated in patients with CDKN2A mutat… (full text at CIViC) PMID 35100714 · Al Baghdadi et al., 2019 · Open in CIViC	civic

CDKN2A Mutation3
(oncogenic)	Burkitt Lymphoma	Oncogenic	E	Supports Oncogenicity	3	submitted	EID11815 Mutations have been described in several studies including the one cited. PMID 30617194 · Grande et al., 2019 · Open in CIViC	civic
Palbociclib	Malignant Pancreatic Neoplasm	Predictive	B	Does Not Support Sensitivity Response	4	accepted	EID7299 In a phase 2 trial, patients with pancreatic cancer with CDKN2A loss or mutation were received palbociclib. Among 12 patients no overall response or stable disease at 16 weeks were observed. Open in CIViC	civic
〃	Cholangiocarcinoma	Predictive	B	Does Not Support Sensitivity Response	4	accepted	EID7300 In a phase 2 trial, patients with gallbladder cancer or bile duct cancer with CDKN2A loss or mutation were received palbociclib. Among 10 patients, no overall response or stable disease at 16 weeks we… (full text at CIViC) Open in CIViC	civic

CDKN2A p16 Expression11
(prognostic)	Malignant Oropharyngeal NeoplasmALIAS	Prognostic	A	Supports Better Outcome	4	accepted	EID758 720 patients with stage III/IV oropharyngeal cancer were retrospectively analyzed for p16 and HPV status. p16 and HPV-positivity correlated well and both showed improved overall-survival compared to p… (full text at CIViC) PMID 20530316 · Ang et al., 2010 · Open in CIViC	civic
〃	Head and Neck Squamous Cell Carcinoma	Prognostic	B	Supports Better Outcome	4	accepted	EID695 p16 positivity, as a surrogate marker for HPV-associated HNSSC was a favorable prognostic marker in recurrent or metastatic carcinoma. PMID 24799460 · Argiris et al., 2014 · Open in CIViC	civic
〃	Head and Neck Squamous Cell Carcinoma	Prognostic	B	Supports Better Outcome	3	accepted	EID804 Patients from three studies (RTOG 0129, 0234, and 0522; 85, 95 and 142 patients, respectively) were retrospectively analyzed for p16 (CDKN2A) expression (IHC) and HPV-high risk status (ISH). p16 expre… (full text at CIViC) PMID 25267748 · Chung et al., 2014 · Open in CIViC	civic
〃	Lung Non-Small Cell CarcinomaCURATED_BROADER	Prognostic	B	Supports Poor Outcome	2	accepted	EID1314 In a cohort of 73 patients with stage I or stage II NSCLC it was discovered that the CDKN2A protein (p16-INK4A) retrospectively evaluated via IHC was associated with adverse outcomes (p=0.004). PMID 22619677 · Zhao et al., 2012 · Open in CIViC	civic
Afatinib	Head and Neck Squamous Cell Carcinoma	Predictive	B	Supports Resistance	2	accepted	EID1155 Phase III trial to compare afatinib or metothrexate in recurrent or metastatic head and neck squamous cell carcinoma. 483 patients were randomized to either afatinib (n=322) or methotrexate (n=161). 2… (full text at CIViC) PMID 25892145 · Machiels et al., 2015 · Open in CIViC	civic
Cetuximab	Head and Neck Squamous Cell Carcinoma	Predictive	B	Does Not Support Resistance	4	accepted	EID697 In this study response to EGFR-inhibition by cetuximab was independent of HPV-status, represented by expression of p16 (CDKN2A, an established biomarker of HPV infection). Expression of p16 was assaye… (full text at CIViC) PMID 24577089 · Pogorzelski et al., 2014 · Open in CIViC	civic
〃	Malignant Oropharyngeal NeoplasmALIAS	Predictive	B	Does Not Support Resistance	4	accepted	EID759 This study shows that benefit of EGFR inhibition in addition to radiotherapy was independent of p16/HPV status. 182 patients were evaluated. PMID 26712222 · Rosenthal et al., 2016 · Open in CIViC	civic
Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor	Head and Neck Squamous Cell Carcinoma	Predictive	B	Does Not Support Resistance	3	accepted	EID694 In this retrospective analysis of the SPECTRUM trial, p16 (CDKN2A) expression (and HPV-infection) was not predictive of response to EGFR-targeted therapy in combination with chemotherapy (n = 416 pati… (full text at CIViC) PMID 24577117 · Vermorken et al., 2014 · Open in CIViC	civic
Palbociclib	Sarcoma	Predictive	D	Supports Resistance	4	submitted	EID4873 A preclinical study to explore the efficacy of CDK4/6 inhibition with palbociclib, in a panel of sarcoma cell lines and sarcoma tumor xenografts (PDXs). The responsiveness of these cell lines/PDX corr… (full text at CIViC) PMID 26528855 · Perez et al., 2015 · Open in CIViC	civic
Panitumumab	Head and Neck Squamous Cell Carcinoma	Predictive	B	Supports Resistance	3	accepted	EID696 In this retrospective analysis of p16 status as surrogate marker for HPV in the SPECTRUM trial, p16 (CDKN2A) expression was not associated with improved response to EGFR-directed therapy (Panitumumab)… (full text at CIViC) PMID 23746666 · Vermorken et al., 2013 · Open in CIViC	civic
〃	Head and Neck Squamous Cell Carcinoma	Predictive	B	Supports Sensitivity Response	3	accepted	EID753 p16-negative patients (HPV negative) have a longer overall survival under panitumumab/chemotherapy in comparison to chemotherapy alone. PMID 23746666 · Vermorken et al., 2013 · Open in CIViC	civic