Diseases Commons^™

5-Hydroxymethylcytosine Localizes To Enhancer Elements And Is Associated With Survival In Glioblastoma Patients, Kevin C. Johnson, E. Andres Houseman, Jessica E. King, Katharine M. Von Herrmann, Camilo E. Fadu, Brock C. Christensen

Dartmouth Scholarship

Glioblastomas exhibit widespread molecular alterations including a highly distorted epigenome. Here, we resolve genome-wide 5-methylcytosine and 5-hydroxymethylcytosine in glioblastoma through parallel processing of DNA with bisulfite and oxidative bisulfite treatments. We apply a statistical algorithm to estimate 5-methylcytosine, 5-hydroxymethylcytosine and unmethylated proportions from methylation array data. We show that 5-hydroxymethylcytosine is depleted in glioblastoma compared with prefrontal cortex tissue. In addition, the genomic localization of 5-hydroxymethylcytosine in glioblastoma is associated with features of dynamic cell-identity regulation such as tissue-specific transcription and super-enhancers. Annotation of 5-hydroxymethylcytosine genomic distribution reveal significant associations with RNA regulatory processes, immune function, stem cell maintenance and …

Constitutively Activated Pi3k Accelerates Tumor Initiation And Modifies Histopathology Of Breast Cancer, M. R. Sheen, J. D. Marotti, M. J. Allegrezza, M. Rutkowski, J. R. Conejo-Garcia, S. Fiering

Dartmouth Scholarship

The gene encoding phosphatidylinositol 3-kinase catalytic subunit α-isoform (PIK3CA, p110α) is frequently activated by mutation in human cancers. Based on detection in some breast cancer precursors, PIK3CA mutations have been proposed to have a role in tumor initiation. To investigate this hypothesis, we generated a novel mouse model with a Cre-recombinase regulated allele of p110α (myristoylated-p110α, myr-p110α) along with p53fl/fl deletion and KrasG12D also regulated by Cre-recombinase. After instillation of adenovirus-expressing Cre-recombinase into mammary ducts, we found that myr-p110α accelerated breast tumor initiation in a copy number-dependent manner. Breast tumors induced by p53fl/fl;KrasG12D with no or one copy of myr-p110α …

Application Of Rnai-Induced Gene Expression Profiles For Prognostic Prediction In Breast Cancer, Yue Wang, Kenneth . M. K. Mark, Matthew H. Ung, Arminja Kettenbach, Todd Miller, Wei Xu, Wenqing Cheng Cheng, Tian Xia, Chao Cheng

Dartmouth Scholarship

Homologous recombination (HR) is the primary pathway for repairing double-strand DNA breaks implicating in the development of cancer. RNAi-based knockdowns of BRCA1 and RAD51 in this pathway have been performed to investigate the resulting transcriptomic profiles. Here we propose a computational framework to utilize these profiles to calculate a score, named RNA-Interference derived Proliferation Score (RIPS), which reflects cell proliferation ability in individual breast tumors. RIPS is predictive of breast cancer classes, prognosis, genome instability, and neoadjuvant chemosensitivity. This framework directly translates the readout of knockdown experiments into potential clinical applications and generates a robust biomarker in breast cancer.

Elevated Mtss1 Expression Associated With Metastasis And Poor Prognosis Of Residual Hepatitis B-Related Hepatocellular Carcinoma, Xiu-Yan Huang, Zi-Li Huang, Bin Xu, Zi Chen

Dartmouth Scholarship

Background: Hepatectomy generally offers the best chance of long-term survival for patients with hepatocellular carcinoma (HCC). Many studies have shown that hepatectomy accelerates tumor metastasis, but the mechanism remains unclear.

Methods: An orthotopic nude mice model with palliative HCC hepatectomy was performed in this study. Metastasis-related genes in tumor following resection were screened; HCC invasion, metastasis, and some molecular alterations were examined in vivo and in vitro. Clinical significance of key gene mRNA expression was also analyzed.

Human Papillomavirus Infection In Rwanda At The Moment Of Implementation Of A National Hpv Vaccination Programme, Fidele Ngabo, Silvia Franceschi, Iacopo Baussano, M. Chantal Umulisa, Peter Snijders, Anne Uyterlinde, Fulvio Lazzarato, Vanessa Tenet, Maurice Gatera, Agnes Binagwaho, Gary Clifford

Dartmouth Scholarship

Cervical cancer is the most common female cancer in Rwanda that, in 2011, became the first African country to implement a national vaccination programme against human papillomavirus (HPV). To provide a robust baseline for future evaluations of vaccine effectiveness, cervical cell specimens were obtained from 2508 women aged 18–69 years from the general population in Kigali, Rwanda, during 2013/14. 20 % of women were HIV-positive. Samples were used for liquid-based cytology and HPV testing (44 types) with GP5+/6+ PC.