ArticleCell cycle (Georgetown, Tex.)2015
Cyclin-dependent kinase pathway aberrations in diverse malignancies: clinical and molecular characteristics.
Article in Cell cycle (Georgetown, Tex.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.
- Unique characteristics ofSaudi journal of gastroenterology : official journal of the Saudi Gastroenterology AssociationPooled it
- Palbociclib in Solid Tumor Patients With Genomic Alterations in the cyclinD-cdk4/6-INK4a-Rb Pathway: Results From National Cancer Institute-Children's Oncology Group Pediatric Molecular Analysis for Therapy Choice Trial Arm I (APEC1621I).JCO precision oncology · 2024Trial
- Molecular profiling of cancer patients enables personalized combination therapy: the I-PREDICT study.Nature medicine · 2019Trial
- Review
- Functional Germline DNA Repair Mutations as Predictors of Acute Radiodermatitis in Breast Cancer.Diagnostics (Basel, Switzerland) · 2026Article
- A retrospective study on the mechanism underlying quick transfer from response to resistance in a repeated recurrent chordoma patient with molecular alterations treated with Palbociclib.Journal of cancer research and clinical oncology · 2024Article
- Deoxyribonucleic acid methylation driven aberrations in pancreatic cancer-related pathways.World journal of gastrointestinal oncology · 2023Review
- Comprehensive Landscape of Cyclin Pathway Gene Alterations and Co-occurrence with FGF/FGFR Aberrations Across Urinary Tract Tumors.The oncologist · 2023Article
- Expression patterns and therapeutic implications of CDK4 across multiple carcinomas: a molecular docking and MD simulation study.Medical oncology (Northwood, London, England) · 2022Article
- INK4 Tumor Suppressor Proteins Mediate Resistance to CDK4/6 Kinase Inhibitors.Cancer discovery · 2022Article
- Concomitant MEK and Cyclin Gene Alterations: Implications for Response to Targeted Therapeutics.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Article
- Targeting G1/S phase cell-cycle genomic alterations and accompanying co-alterations with individualized CDK4/6 inhibitor-based regimens.JCI insight · 2021Article
- Cyclin Pathway Genomic Alterations Across 190,247 Solid Tumors: Leveraging Large-Scale Data to Inform Therapeutic Directions.The oncologist · 2021Article
- The role of histone methylation in the development of digestive cancers: a potential direction for cancer management.Signal transduction and targeted therapy · 2020Review
- Tissue gene mutation profiles in patients with colorectal cancer and their clinical implications.Biomedical reports · 2020Article
- Human Papillomaviruses and Epstein-Barr Virus Interactions in Colorectal Cancer: A Brief Review.Pathogens (Basel, Switzerland) · 2020Review
- Multiple Molecular Targets Associated with Genomic Instability in Lung Cancer.International journal of genomics · 2019Review
- Prospective Longitudinal ctDNA Workflow Reveals Clinically Actionable Alterations in Ovarian Cancer.JCO precision oncology · 2019Article
- Cyclin E Overexpression Sensitizes Triple-Negative Breast Cancer to Wee1 Kinase Inhibition.Clinical cancer research : an official journal of the American Association for Cancer Research · 2018Article
- Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aberrations in the cyclin-dependent kinase (CDK) pathways that regulate the cell cycle restriction point contribute to genomic instability and tumor proliferation, and can be targeted by recently developed CDK inhibitors. We therefore investigated the clinical correlates of CDK4/6 and CDKN2A/B abnormalities in diverse malignancies. Patients with various cancers who underwent molecular profiling by targeted next generation sequencing (Foundation Medicine; 182 or 236 cancer-related genes) were reviewed. Of 347 patients analyzed, 79 (22.8%) had aberrant CDK 4/6 or CDKN2A/B. Only TP53 mutations occurred more frequently than those in CDK elements. Aberrations were most frequent in glioblastomas (21/26 patients; 81%) and least frequent in colorectal cancers (0/26 patients). Aberrant CDK elements were independently associated with EGFR and ARID1A gene abnormalities (P < 0.0001 and p = 0.01; multivariate analysis). CDK aberrations were associated with poor overall survival (univariate analysis; HR[95% CI] = 2.09 [1.35-4.70]; p = 0.004). In multivariate analysis, PTEN and TP53 aberrations were independently associated with poorer survival (HR = 4.83 and 1.92; P < 0.0001 and p = 0.01); CDK aberrations showed a trend toward worse survival (HR = 1.67; p = 0.09). There was also a trend toward worse progression-free survival (PFS) with platinum-containing regimens in patients with abnormal CDK elements (3.5 versus 5.0 months, p = 0.13). In conclusion, aberrations in the CDK pathway were some of the most common in cancer and independently associated with EGFR and ARID1A alterations. Patients with abnormal CDK pathway genes showed a trend toward poorer survival, as well as worse PFS on platinum-containing regimens. Further investigation of the prognostic and predictive impact of CDK alterations across cancers is warranted.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.