OBJECTIVES/HYPOTHESIS To determine the incidence and clinical significance of TP53 and CDKN2a somatic mutations in never smokers with oral tongue squamous cell carcinoma (OTSCC). STUDY DESIGN Case series. METHODS Fifty-one paraffin-embedded tumors from never smokers with OTSCC were obtained. p53 and p16 expression was determined by immunohistochemical (IHC) staining. Tumor DNA was amplified...

The molecular events in chordoma pathogenesis have not been fully delineated, particularly with respect to copy number changes. Understanding copy number alterations in chordoma may reveal critical disease mechanisms that could be exploited for tumor classification and therapy. We report the copy number analysis of 21 sporadic chordomas using array comparative genomic hybridization (CGH). Recur...

In this study, we analyzed the genetic profiles of squamous cell lung carcinoma (SqCLC) to identify potential therapeutic targets. Approximately 2,800 COSMIC mutations from 50 genes were determined by next-generation sequencing. Amplification/deletion of SOX2, CDKN2A, PTEN, FGFR1, EGFR, CCND1, HER2 and PDGFRA were detected by FISH and expression of VEGFR2, PD-L1 and PTEN were examined by IHC. O...

Patients with chronic kidney disease (CKD) display a progeric vascular phenotype linked to apoptosis, cellular senescence and osteogenic transformation. This has proven intractable to modelling appropriately in model organisms. We have therefore investigated this directly in man, using for the first time validated cellular biomarkers of ageing (CDKN2A/p16INK4a, SA-β-Gal) in arterial biopsies fr...

Cellular senescence is a crucial tumor suppressor mechanism. We discovered a CAPERα/TBX3 repressor complex required to prevent senescence in primary cells and mouse embryos. Critical, previously unknown roles for CAPERα in controlling cell proliferation are manifest in an obligatory interaction with TBX3 to regulate chromatin structure and repress transcription of CDKN2A-p16INK and the RB pathw...

Glioblastomas (GBMs) are deadly tumors of the central nervous system. Most GBM exhibit homozygous deletions of the CDKN2A and CDKN2B tumor suppressors at 9p21.3, although loss of CDKN2A/B alone is insufficient to drive gliomagenesis. MIR31HG, which encodes microRNA-31 (miR-31), is a novel non-coding tumor suppressor positioned adjacent to CDKN2A/B at 9p21.3. We have determined that miR-31 expre...

Familial atypical multiple mole melanoma syndrome (FAMMM) is characterised by dysplastic naevi, malignant melanoma and pancreatic cancer. Given that large deletions involving CDKN2A (cyclin-dependent kinase inhibitor 2A) account for only 2% of cases, we describe a family that highlights the co-occurrence of both melanoma and neural system tumours to aid clinical recognition and propose a manage...

Gliomas are most common neoplasms in the CNS with unknown aetiology. Gene polymorphisms have been studied in glioma to check its risk in different population. CDKN2A, commonly altered tumor suppressor gene polymorphisms were recently shown to be associated with glioma in Caucasians. Present study evaluated potential association between two SNPs in CDKN2A/B gene with glioma risk in South Indian ...

Background: Several studies were performed to investigate the association between CDKN2A/B rs4977756 polymorphism and the risk of glioma. However, the results were inconsistent. Thus, we performed this meta-analysis. Methods: Eleven studies including 12814 glioma patients and 21140 controls were included in the meta-analysis. The pooled odds ratio (OR) and its corresponding 95% confidence inter...