BACKGROUND Atypical squamous cell cannot exclude high-grade squamous intraepithelial lesion (ASC-H) and low-grade intraepithelial lesion cannot exclude high-grade squamous intraepithelial lesion (LSIL-H) are ambiguous diagnostic entities for the prediction of high-grade cervical lesion. Objective and reproducible tests for predicting high-grade cervical lesions are needed to reduce unnecessary ...

The CDKN2A/ARF locus encompasses overlapping tumor suppressor genes p16(INK4A) and p14(ARF), which are frequently co-deleted in human malignant mesothelioma (MM). The importance of p16(INK4A) loss in human cancer is well established, but the relative significance of p14(ARF) loss has been debated. The tumor predisposition of mice singly deficient for either Ink4a or Arf, due to targeting of exo...

BACKGROUND The INK4A and INK4B genes map to chromosome 9p21, with the INK4A gene encoding two protein products, p16 and pl9ARF. Alterations of the INK4A and INK4B genes occur frequently in certain primary malignant neoplasms. This study was undertaken to evaluate the frequency of INK4A and INK4B gene alterations in a cohort of adult soft tissue sarcomas. METHODS The status of the INK4A and IN...

AIM To characterize the immunohistochemical expression of p27, p21(WAF/Cip1) and p16(INK4a) in normal oral epithelium, oral squamous papilloma and oral squamous cell carcinoma. MATERIALS AND METHODS Immunohistochemical staining for p27, p21(WAF/Cip1) and p16(INK4a) was evaluated in 32 samples of normal oral squamous epithelium, 30 samples of oral squamous papilloma, and 34 samples of oral squ...

The molecular mechanisms underlying the pathogenesis of aggressive lymphomas and the histological transformation of indolent variants are not well known. To determine the role of p16(INK4a) gene alterations in the pathogenesis of non-Hodgkin's lymphomas (NHLs) and the histological progression of indolent variants, we have analyzed the expression, deletions, and mutations of this gene in a serie...

The molecular mechanisms that lead to tubular atrophy, capillary loss, and fibrosis following acute kidney injury are not very clear but may involve cell cycle inhibition by increased expression of cyclin kinase inhibitors. The INK4a/ARF locus encodes overlapping genes for two proteins, a cyclin kinase inhibitor, p16(INK4a), and a p53 stabilizer, p19(ARF), from independent promoters. To determi...

PURPOSE EGR-1 is an immediate early gene with diverse functions that include the suppression of growth. EGR-1 is down-regulated many cancer cell types, suggesting a tumor suppressor role, and may critically involve the p53 pathway. The aim of this work was to measure the expression of EGR-1 and the p16/INK4a/ARF-Mdm2-p53 pathway status in fresh human gliomas. EXPERIMENTAL DESIGN Thirty-one hu...

PURPOSE The chromosome 9p21 region harbors three tumor suppressor genes, p14(ARF), p15(INK4b), and p16(INK4a), all of which can be targets for hypermethylation-associated inactivation in low-grade gliomas. p16(INK4a) and p15(INK4b) are critically involved in the RB1 pathway, whereas p14(ARF) acts as an upstream regulator of the TP53 pathway. The role of each tumor suppressor pathway in low-grad...

PURPOSE BRAF is frequently activated by gene fusion or point mutation in pilocytic astrocytoma, the most common pediatric brain tumor. We investigated the functional effect of constitutive BRAF activation in normal human neural stem and progenitor cells to determine its role in tumor induction in the brain. EXPERIMENTAL DESIGN The constitutively active BRAF(V600E) allele was introduced into h...

Gene amplification is a relatively rare event in hematologic malignancies. The ABL gene on chromosome band 9q34 is a proto-oncogene and is the well-known translocation partner of the BCR gene on 22q11 giving rise to t(9;22)(q34;q11), which is the hallmark of chronic myeloid leukemia and is the most common chromosomal abnormality in adult acute lymphoblastic leukemia (ALL). Amplification of ABL ...