Novel Common Genetic Susceptibility Loci for Colorectal Cancer.

Background: Previous genome-wide association studies (GWAS) have identified 42 loci (P < 5 × 10-8) associated with risk of colorectal cancer (CRC). Expanded consortium efforts facilitating the discovery of additional susceptibility loci may capture unexplained familial risk.

Methods: We conducted a GWAS in European descent CRC cases and control subjects using a discovery-replication design, followed by examination of novel findings in a multiethnic sample (cumulative n = 163 315).

Evidence of altered brain regulatory gene expression in tobacco-exposed fetuses.

Aim: We sought to determine the association between prenatal smoking status and expression of fetal brain regulatory genes.

Methods: At delivery, we collected information from parturient women on prenatal smoking habits and analyzed salivary cotinine levels. We obtained neonatal umbilical cord blood and extracted total RNA.

A positive association between umbilical cord RBC folate and fetal TL at birth supports a potential for fetal reprogramming.

Telomere length (TL) has been studied extensively in adults; however, limited information exists regarding maternal influences on TL in utero. The objective of this study was to investigate the relationship between fetal red blood cell (RBC) folate levels, a surrogate measure for maternal folate levels, and TL. We hypothesized that umbilical cord RBC folate concentrations would positively correlate with fetal TL.

Homocysteine Levels Are not Related to Telomere Length in Cord Blood Leukocytes of Newborns.

Objective Elevated homocysteine (HC) levels and/or shortened telomere length (TL) are associated with adverse medical conditions. Our objective is to investigate the relationship between HC and TL in cord blood leukocytes of newborns. Study Design This is a nested study from a prospective cohort from 2011 to 2012 in pregnant women admitted for delivery at a university-affiliated hospital.

Quantitative DNA methylation analysis of candidate genes in cervical cancer.

Aberrant DNA methylation has been observed in cervical cancer; however, most studies have used non-quantitative approaches to measure DNA methylation. The objective of this study was to quantify methylation within a select panel of genes previously identified as targets for epigenetic silencing in cervical cancer and to identify genes with elevated methylation that can distinguish cancer from normal cervical tissues. We identified 49 women with invasive squamous cell cancer of the cervix and 22 women with normal cytology specimens.

Expanding epigenomics to archived FFPE tissues: an evaluation of DNA repair methodologies.

Background: Epigenome-wide association studies are emerging in the field of cancer epidemiology with the rapid development of large-scale methylation array platforms. Until recently, these methods were only valid for DNA from flash frozen (FF) tissues. Novel techniques for repairing DNA from formalin-fixed paraffin-embedded (FFPE) tissues have emerged; however, a direct comparison of FFPE DNA repair methods before analysis on genome-wide methylation array to matched FF tissues has not been conducted.

Epigenomic characterization of locally advanced anal cancer: a radiation therapy oncology group 98-11 specimen study.

Background: The Radiation Therapy Oncology Group 98-11 clinical trial demonstrated the superiority of standard 5-fluorouracil/mitomycin-C over 5-fluorouracil/cisplatin in combination with radiation in the treatment of anal squamous cell cancer. Tumor size (>5 cm) and lymph node metastases are associated with disease progression. There may be key molecular differences (eg, DNA methylation changes) in tumors at high risk for progression.

DNA methylation profiling across the spectrum of HPV-associated anal squamous neoplasia.

Background: Changes in host tumor genome DNA methylation patterns are among the molecular alterations associated with HPV-related carcinogenesis. However, there is little known about the epigenetic changes associated specifically with the development of anal squamous cell cancer (SCC). We sought to characterize broad methylation profiles across the spectrum of anal squamous neoplasia.

WIF1 is a frequent target for epigenetic silencing in squamous cell carcinoma of the cervix.

Aberrant activation of the Wnt/β-catenin signaling axis is a prominent oncogenic mechanism in numerous cancers including cervical cancer. Wnt inhibitory factor-1 (WIF1) is a secreted protein that binds Wnt and antagonizes Wnt activity. While the WIF1 gene is characterized as a target for epigenetic silencing in some tumor types, WIF1 expression has not been examined in human cervical tissue and cervical cancer.

Phosphatidylinositol synthase of Tetrahymena: inositol isomers as substrates in phosphatidylinositol biosynthesis and headgroup exchange reactions.

Phosphatidylinositol (PtdIns) synthase in microsomal fractions derived from Tetrahymena vorax was studied to determine its activity requirements. The suitability of inositol isomers as substrates for the synthase and in headgroup exchange reactions also was investigated. Tetrahymena PtdIn synthase activity was optimum in the presence of 2 mM MgCl2 plus 2 mM MnCl2, a pH of 7.

Phospholipids of the differentiating species of Tetrahymena.

The whole-cell phospholipid composition of the six known polymorphic species of Tetrahymena has been examined by [(3)H]acetate and [(3)H]myristic acid radiolabeling, and by gas-liquid chromatography of total phospholipid-bound fatty acids. Five of the polymorphic species contained similar phospholipid profiles following radiolabeling in that phosphatidylethanolamine (PE) was the predominant phospholipid; however, in cells of Tetrahymena patula LFF, aminoethylphosphonolipid was present in amounts nearly equal to PE. Tetrahymena patula LFF contained an unusually large percentage of sphingolipid (16.

Molecular determinants of the response of glioblastomas to EGFR kinase inhibitors.

Background: The epidermal growth factor receptor (EGFR) is frequently amplified, overexpressed, or mutated in glioblastomas, but only 10 to 20 percent of patients have a response to EGFR kinase inhibitors. The mechanism of responsiveness of glioblastomas to these inhibitors is unknown.

Methods: We sequenced kinase domains in the EGFR and human EGFR type 2 (Her2/neu) genes and analyzed the expression of EGFR, EGFR deletion mutant variant III (EGFRvIII), and the tumor-suppressor protein PTEN in recurrent malignant gliomas from patients who had received EGFR kinase inhibitors.