William B. Chapman

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Epigenetic mechanisms of gene silencing, including promoter hypermethylation of tumor suppressor genes, have been shown to contribute to tumorigenesis. PTEN is an important tumor suppressor implicated in the pathogenesis of a number of familial and sporadic cancers. Germline mutations of PTEN predispose to dominantly inherited hamartomatous disorders Cowden(More)
To determine the relationship between the expression of epidermal growth factor receptor (EGFR) and the presence or type of human papillomavirus (HPV) in cervical squamous intraepithelial lesions (SIL), paired colposcopically directed cervical biopsies were obtained from 88 patients referred for abnormal Papanicolaou smears. One biopsy was formalin-fixed(More)
Several recent advances have been made in our understanding of the pathogenesis of endometrial tumours, particularly endometrioid endometrial carcinoma (EEC). Mutations in the PTEN gene and microsatellite instability (MSI) are common genetic abnormalities in EECs, and distinguish these lesions from other histological subtypes of endometrial carcinoma.(More)
In order to determine the distribution of human papillomavirus (HPV) types and to compare in situ hybridization (ISH) with Southern blot hybridization (SBH), paired colposcopically directed cervical biopsies and cervical-vaginal lavages were obtained from 92 women referred for abnormal Pap smears. The lavages and one of the biopsies were snap-frozen and(More)
PTEN is a tumor suppressor gene mutated in various advanced human neoplasias, including glioblastomas and prostate, breast, endometrial, and kidney cancers. This tumor suppressor is a lipid phosphatase that negatively regulates cell survival and proliferation mediated by phosphatidylinositol 3-kinase/protein kinase B signaling. Using the Cre-loxP system, we(More)
Microsatellite instability (MSI) is observed in a subset of endometrial cancers (ECs) and is attributed to defects in mismatch repair. Mismatch repair deficiency allows for accumulation of mutations in the coding repeats of key target genes, which may be involved in the initiation and progression of MSI+ EC. We examined genes implicated in DNA repair(More)
The presence of cell surface receptor glycolipid, globotriaosylceramide (Gb3), is essential to confer susceptibility to the E. coli-derived verotoxin (VT). Our earlier studies showed that Gb3 is expressed in ovarian carcinoma cell lines. The Gb3 content of normal ovary, benign and malignant primary ovarian tumors, and their metastases have now been compared(More)
Differential methylation is an important epigenetic control mechanism, which has been implicated in the development of a variety of cancers. Methylation of promoter regions of normally unmethylated tumor suppressor genes leads to transcriptional inactivation and ultimately to tumor formation. We hypothesized that epigenetic inactivation of adenomatous(More)
Primary vulvar adenocarcinomas are rare tumors, and their histogenesis is not fully understood. They are classified into extramammary Paget's disease, sweat gland carcinomas, and "breast-like" adenocarcinomas of the vulva. The latter resemble adenocarcinomas arising in the breast morphologically and immunophenotypically. Rare cases of adenocarcinoma with(More)
Among multiple genetic pathways involved in endometrial cancer (EC), the mutator pathway is characterized by defective mismatch repair (MMR) causing microsatellite instability (MSI+). Inactivation of MMR genes allows elevation of mutation rates in key target genes involved in important cellular pathways, providing a selective growth advantage. Our aim was(More)