cdkn2a - Histology

What is CDKN2A?

CDKN2A is a gene located on chromosome 9p21 that plays a crucial role in regulating the cell cycle. It encodes two important proteins: p16INK4a and p14ARF through alternative splicing. These proteins are pivotal in controlling cellular proliferation by inhibiting cyclin-dependent kinases (CDKs), thus preventing the progression of the cell cycle from G1 to S phase.

Role in Cell Cycle Regulation

The p16INK4a protein inhibits CDK4 and CDK6, leading to the stabilization of the retinoblastoma (RB) protein, which in turn prevents the cell from progressing from the G1 phase to the S phase of the cell cycle. This inhibition is a key mechanism for preventing uncontrolled cell proliferation, which is a hallmark of cancer. On the other hand, p14ARF interacts with the MDM2 protein to stabilize p53, a tumor suppressor protein that can induce cell cycle arrest or apoptosis in response to DNA damage.

Implications in Cancer

Mutations or deletions in the CDKN2A gene are commonly associated with various types of cancer, including melanoma, pancreatic cancer, and glioblastoma. Loss of function of CDKN2A leads to dysregulation of the cell cycle, allowing cells to proliferate uncontrollably. Therefore, CDKN2A is considered a significant tumor suppressor gene.

Histological Examination

In histology, the expression of CDKN2A can be examined using immunohistochemistry (IHC). IHC staining for p16INK4a is often used to assess the status of CDKN2A in tissue samples. For example, in cervical biopsies, overexpression of p16INK4a can be indicative of high-risk human papillomavirus (HPV) infection and the potential for neoplastic transformation.

Clinical Applications

Understanding the status of CDKN2A can have significant clinical implications. It can be used as a diagnostic marker to identify pre-cancerous lesions or to predict the prognosis of certain cancers. Moreover, targeted therapies that aim to restore the function of the CDKN2A pathway are an area of ongoing research, offering potential for new treatment strategies.

Research and Future Directions

Research into CDKN2A continues to uncover its complex role in cell cycle regulation and cancer. Studies are exploring how CDKN2A interacts with other cell cycle regulators and how its function can be modulated to develop new therapeutic approaches. Additionally, the use of genetic and epigenetic techniques to restore or compensate for the loss of CDKN2A function holds promise for future cancer treatments.

Relevant Publications

Comprehensive characterization of intraductal oncocytic papillary neoplasm (IOPN) of the pancreas: a systematic and critical review.

Issue Release: 2024

Genomic profiles of Japanese patients with vulvar squamous cell carcinoma.

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DNA Mutational and Copy Number Variation Profiling of Primary Craniofacial Osteosarcomas by Next-Generation Sequencing.

Issue Release: 2024

Study on the anti-skin aging effect and mechanism of Sijunzi Tang based on network pharmacology and experimental validation.

Issue Release: 2024

Revealing the key role of cuproptosis in osteoporosis via the bioinformatic analysis and experimental validation of cuproptosis-related genes.

Issue Release: 2024

The impact of comparative genomic hybridization/single-nucleotide polymorphism microarray in risk stratification of pediatric acute lymphoblastic leukemia.

Issue Release: 2024

T2-FLAIR mismatch sign, an imaging biomarker for CDKN2A-intact in non-enhancing astrocytoma, IDH-mutant.

Issue Release: 2024

Prevalence of CDKN2A, CDK4, POT1, BAP1, MITF, ATM, and TERT Pathogenic Variants in a Single-Center Retrospective Series of Patients With Melanoma and Personal or Family History Suggestive of Genetic Predisposition.

Issue Release: 2024

Duodenal Fluid Analysis as a Rewarding Approach to Detect Low-Abundance Mutations in Biliopancreatic Cancers.

Issue Release: 2024

The role of palbociclib on the alterations in CDKN2, CCNE1, E2F3, MDM2 expressions as target genes of miR-141.

Issue Release: 2024

Exploring the relationship between anal fistula and colorectal cancer based on Mendelian randomization and bioinformatics.

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Pleomorphic xanthoastrocytoma with NTRK fusion presenting as spontaneous intracranial hemorrhage-case report and literature review.

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Poor prognosis among radiation associated bladder cancer is defined by clinicogenomic features.

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Lung-MAP Next Generation Sequencing Analysis of Advanced Squamous Cell Lung Cancers (SWOG S1400).

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Mesothelioma: molecular pathology and biomarkers.

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[Advances in Targeted Therapy for Malignant Pleural Mesothelioma].

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Distinct cuproptosis patterns in hepatocellular carcinoma patients correlate with unique immune microenvironment characteristics and cell-cell communication, contributing to varied overall survival outcomes.

Issue Release: 2024

Identification of 10 differentially expressed and cuproptosis-related genes in immune infiltration and prognosis of thyroid carcinoma.

Issue Release: 2024

UHRF1 poly-auto-ubiquitination induced by the anti-cancer drug, thymoquinone, is involved in the DNA repair machinery recruitment.

Issue Release: 2024

Vasospasm and subsequent stroke from paraneoplastic syndrome in a pediatric patient with an intracranial mature teratoma: a case report.

Issue Release: 2024

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