CDK4, cyclin dependent kinase 4, 1019

N. diseases: 433; N. variants: 8
Source: ALL
Disease Score gda Association Type Type Original DB Sentence supporting the association PMID PMID Year
CUI: C0025202
Disease: melanoma
melanoma 		0.700 GeneticVariation disease BEFREE Here, we generated T cells expressing a mutation-specific transgenic T cell receptor (TCR) to target different immunogenic mutations in cyclin-dependent kinase 4 (CDK4) that naturally occur in human melanoma. 26808500 2016
CUI: C0025202
Disease: melanoma
melanoma 		0.700 GeneticVariation disease BEFREE These data strongly support the idea that deregulation of the CDK4/cyclin D pathway, via CDKN2 or CDK4 mutations, is of biological significance in the development of melanoma. 9036865 1997
CUI: C0025202
Disease: melanoma
melanoma 		0.700 GeneticVariation disease BEFREE Mutations in CDK4 that impair the inhibitory interaction with p16INK4a also increase melanoma risk but these mutations are extremely rare. 24258989 2014
CUI: C0025202
Disease: melanoma
melanoma 		0.700 GeneticVariation disease BEFREE In the case of CDK4, only one specific mutation, resulting in the substitution of a cysteine for an arginine at codon 24 (R24C), has been found to be associated with melanoma. 9416844 1997
CUI: C0025202
Disease: melanoma
melanoma 		0.700 GeneticVariation disease BEFREE Less frequently, germline mutations in the CDK4 gene have also been linked with an increased risk of melanoma. 10777219 2000
CUI: C0025202
Disease: melanoma
melanoma 		0.700 GeneticVariation disease BEFREE Nearly 100% of melanomas have a defect in the p16(INK4A):cyclin D-CDK4/6:RB pathway, leading to abnormal cell cycle control and unregulated cellular proliferation. 26810603 2016
CUI: C0025202
Disease: melanoma
melanoma 		0.700 GeneticVariation disease CLINVAR Prospective enterprise-level molecular genotyping of a cohort of cancer patients. 25157968 2014
CUI: C0025202
Disease: melanoma
melanoma 		0.700 GeneticVariation disease BEFREE No mobility shifts indicating sequence alterations were observed in 273 tumors and 49 cell lines from diverse kinds of tumors These results suggest that in contrast to melanoma, in many other types of human neoplasms the mutation of the CDK4 gene is very rare. 12731669 2003
CUI: C0025202
Disease: melanoma
melanoma 		0.700 GeneticVariation disease BEFREE The cellular activities of four melanoma-associated p16(INK4a) mutations (Arg24Pro, Ala36Pro, Met53Ile, and Val126Asp) were compared by use of inducible expression in stably transfected melanoma cells, deficient in expression of the endogenous protein, and compared with their ability to bind CDK4. 11595726 2001
CUI: C0025202
Disease: melanoma
melanoma 		0.700 GeneticVariation disease BEFREE A proportion of melanoma-prone individuals in both familial and non-familial contexts has been shown to carry inactivating mutations in either CDKN2A or, rarely, CDK4. 12497626 2003
CUI: C0025202
Disease: melanoma
melanoma 		0.700 GeneticVariation disease BEFREE Therefore, to localize additional loci involved in melanoma susceptibility, we have performed a genomewide scan for linkage in 49 Australian pedigrees containing at least three CMM cases, in which CDKN2A and CDK4 involvement has been excluded. 12844286 2003
CUI: C0025202
Disease: melanoma
melanoma 		0.700 GeneticVariation disease BEFREE Germline mutations in the cyclin-dependent kinase gene CDK4 (chromosome 12q14) have been described in three melanoma families. 10630172 1999
CUI: C0025202
Disease: melanoma
melanoma 		0.700 GeneticVariation disease BEFREE Human BRAF-V600-mutant melanoma (A375) xenograft-bearing balb/c nude mice (n = 21) were imaged by <sup>18</sup>F-FDG-PET/CT and DW-MRI before (day 0) and after (day 7) a 1-week BRAF and CDK 4/6 inhibitor combination therapy (n = 12; dabrafenib, 20 mg/kg/d; ribociclib, 100 mg/kg/d) or placebo (n = 9). 29347968 2018
CUI: C0025202
Disease: melanoma
melanoma 		0.700 GeneticVariation disease BEFREE In summary, our results show frequent involvement of the p16 gene in familial melanoma and confirm the role of the CDK4 gene as a melanoma-predisposing gene. 9425228 1998
CUI: C0025202
Disease: melanoma
melanoma 		0.700 GeneticVariation disease BEFREE Polymerase chain reaction and Southern blot analysis confirmed the frequent deletion or rearrangement of the CDK4-inhibitor gene in melanomas, gliomas, lung cancers and leukaemias, and the absence of detectable gene transcripts. 8152487 1994
CUI: C0025202
Disease: melanoma
melanoma 		0.700 GeneticVariation disease BEFREE A CDK4 mutation was found in 89 (including 62 melanoma cases) of 209 tested subjects. 23384855 2013
CUI: C0025202
Disease: melanoma
melanoma 		0.700 GeneticVariation disease BEFREE Mutation profiles of the majority of mucosal melanomas suggest potential susceptibility to CDK4/6 and/or MEK inhibitors. 31320640 2019
CUI: C0025202
Disease: melanoma
melanoma 		0.700 GeneticVariation disease BEFREE The gene for cyclin-dependent kinase 4, CDK4, has been found in mutated form in the germline from individuals belonging to 2 melanoma kindreds in the United States. 9724087 1998
CUI: C0025202
Disease: melanoma
melanoma 		0.700 GeneticVariation disease BEFREE Among patients included in the North Sardinia tumor registry, 316 patients first evaluated for familial recurrence of melanoma were submitted to mutation analysis in CDKN2A and CDK4 genes. 26999380 2017
CUI: C0025202
Disease: melanoma
melanoma 		0.700 GeneticVariation disease BEFREE To examine the contribution of rare and common variation within known MM genes in sporadic US MM patients, coding regions of known MM susceptibility genes [cyclin-dependent kinase inhibitor 2A (CDKN2A), cyclin-dependent kinase 4, melanocortin 1 receptor (MC1R) and tyrosinase (TYR)] were resequenced in 109-135 MM cases. 19320745 2009
CUI: C0025202
Disease: melanoma
melanoma 		0.700 GeneticVariation disease BEFREE Surprisingly, at the DNA level alone, 96% (43/45) of melanoma cell lines examined were found to be deleted/mutated/methylated for CDKN2A (34/45), homozygously deleted for CDKN2A's neighbor and homolog CDKN2B (6/45), and/or mutated/amplified for CDK4 (5/45). 9598804 1998
CUI: C0025202
Disease: melanoma
melanoma 		0.700 GeneticVariation disease BEFREE We identified germline mutations in highly CM-associated genes (CDKN2A and CDK4) and low/medium-penetrance variants (MC1R and MITF) in patients with multiple primary CMs or individuals with one or more CM and a positive family history for CM or pancreatic cancer among first- or second-degree relatives. 27473757 2016
CUI: C0025202
Disease: melanoma
melanoma 		0.700 GeneticVariation disease BEFREE As the pivotal residues around the most predominant R24C activating CDK4 mutation are invariant between CDK2 and CDK4, we speculated that the pivotal arginine (position 22 in CDK2), or a nearby residue, may be mutated in some melanomas, resulting in the diminution of its binding and inhibition by p27KIP1 or p21CIP1. 11479422 2001
CUI: C0025202
Disease: melanoma
melanoma 		0.700 GeneticVariation disease BEFREE Of these, 238 cases (34 familial, 14 non-familial multiple primary and 190 non-familial single primary melanomas) were consecutively enrolled for screening of the CDKN2A and CDK4 genes. 15577313 2004
CUI: C0025202
Disease: melanoma
melanoma 		0.700 GeneticVariation disease LHGDN Thus the phenotype observed in melanoma-prone CDK4 families appears to be more complex than just the CDK4 mutation. 11828258 2002