Day 2 :
Keynote Forum
Gordon Taylor Moffat
SUNY Downstate Medical Center College of Medicine, USA
Keynote: Burden of BRCA1, BRCA 2, and PABL2 Gene Mutations in Caribbean Women with Breast Cancer
Time : 9:30 - 11:00
Biography:
Gordon Moffat has his experience if Life Sciences with an Honors in Biology with training in Radiology. His passion for science and interest in microbiology lead him to pursue and obtain a Doctor of Medicine. Currently he is working at the State University of New York Brooklyn Health Sciences Center in Internal Medicine and the forthcoming Medicine Chief Resident. His professional interests include: Medical Oncology, Hospice and Palliative Medicine, and Geriatric Medicine. He is currently working on research projects at Memorial Sloan Kettering Cancer Center in Manhattan, New York that are expected to be published. He is also a candidate for the Alpha Omega Alpha Honor Medical Society Postgraduate Fellowship Award.
Abstract:
Purpose:
Identifying mutations in breast cancer genes (BRCA1, BRCA2, PABL2) has important clinical implications on a woman's lifetime susceptibility to breast cancer development. Nearly 10% of immigrants to the United States come from the Caribbean and few studies exist that examine breast cancer gene mutations in African-Caribbean women with existing breast cancer. The purpose is to specifically describe breast cancer epidemiology statistics and review prevalence of BRCA mutations in this cohort.
Methods:
Epidemiologic data on select Caribbean countries and USA was abstracted from GLOBOCAN 2012, a database of estimated global cancer statistics produced by the International Agency for Research on Cancer and World Health Organization. Sex-specific age standardized incidence and mortality rates for breast cancer in specific countries are presented in Table 1. A Literature Search was also conducted through PubMed database using following terms: Caribbean , (familial breast cancer), (hereditary breast cancer), and (BRCA breast cancer) that was subsequently narrowed to epidemiologic relevance resulting in five citations and presented in Table 2.
Conclusions:
The GLOBOCAN 2012 data provides an estimate of breast cancer incidence and mortality in Caribbean women. This study summarizes the known prevalence of BRCA1/2 and PALB2 breast cancer gene mutations in select Caribbean cohorts. This is critical as part of a formal genetic risk assessment and counseling of patients with breast cancer, particularly in areas that serve a Caribbean population. Further research and understanding the contributions of inherited gene mutations will guide the optimal health policy in breast cancer screening and risk management.
- Cancer Research and Trials | Cancer Surgery | Cancer Epigenetics | Epigenomic Effects of Environmental Exposures | Epigenetic Biomarkers in Cancer
Chair
Bharat Singh Negi
Kobe University, Japan
Session Introduction
Somnath Pandey
Temple University School of Medicine, Philadelphia, USA
Title: CDK9 phosphorylates BRG1 chromatin remodeler to regulate gene expression
Biography:
He is currently a Post-Doctoral Associate at Temple University School of Medicine, Philadelphia, USA
Abstract:
Cyclin-dependent kinase 9 (CDK9) belongs to the class of CDKs involved in transcription regulation along with CDK7, 8, 10-13. Earlier works have established that CDK9 is the catalytic subunit of P-TEFb, and a transcriptional activator. CDK9 inhibition holds promise for patients belonging to Chronic Lymphocytic Leukemia (CLL) and BRD4-NUT-rearranged NUT midline carcinoma (NMC) groups. It is therefore fundamentally important to understand CDK9 mediated gene regulation. CDK9 in complex with its regulatory subunit, Cyclin T1 or T2, is known to promote RNAPII promoter-proximal pause release by phosphorylating negative elongation factors. Additionally, phosphorylation of the C-terminal domain (CTD) of RNAPII on Serine-2 allows recruitment of RNA processing factors, which work on the nascent RNA as it emerges from RNAPII. It is however not known whether CDK9 has any transcriptional repression activity. Earlier work from our lab demonstrated that long-term CDK9 inhibition leads to the activation of BRG1, an ATP-dependent nucleosome-remodeling complex from the SWI/SNF family of proteins. We therefore hypothesized that CDK9 directly phosphorylates BRG1 and regulates its activity. Using Co-immunoprecipitation (Co-IP) assay we discovered that CDK9 associates with BRG1 endogenously in colon cancer cells. We tested the association of these proteins more rigorously by transiently over-expressing either FLAG-tagged or GFP-tagged CDK9 in HEK293T cells and performed immunoprecipitation using BRG1 antibody. CDK9 was found to co-precipitate with BRG1. We validated this via reciprocal Co-IPs. We performed an in vitro kinase assay using purified CDK9 and BRG1 proteins to demonstrate that CDK9 directly phosphorylates BRG1 and that inhibition of CDK9 leads to reduced phosphorylation of BRG1. We validated these results in vivo in colon cancer cells. Furthermore, our LC-MS/MS data lead to the identification of novel phosphorylation sites in BRG1 following CDK9 inhibition. These findings provide a potential mechanism for the transcriptional repressor activity associated with CDK9 and may be relevant for developing therapies targeting this transcriptional regulator.
Xiaoying Cui
The University of Queensland, Australia
Title: Noncoding RNA regulation of neuroblastoma growth and apoptosis via epigenetic pathways
Biography:
Xiaoying Cui has completed her PhD in 2004 from Harbin Medical University and Singapore General Hospital. Her postdoctoral studies are at the Queensland Brain Institute, the University of Queensland. She is currently a senior research fellow in the Neurodevelopmental Group in the Queensland Brain Institute. She has published more than 31 papers in reputed journals, which attracted over 1480 citations (Google Scholar) and has been serving as reviewer for multiple renowned journals.
Abstract:
Neuroblastoma is a severe disorder that affects infant and young children. The survival rates of the patients with highly aggressive tumour is less than 50%, despite intensive multimodal therapy. Recently, a growth body of evidence have shown that noncoding RNAs played critical role in the tumour growth and are now the novel drug targets for multiple tumours. Long intergenic noncoding RNA HOX-antisense intergenic RNA myeloid 1 (HOTAIRM1) had been found to be associated with a few cancers including leukemia, colon cancer and breast cancer. In this study, we showed that low HOTAIRM1 was expressed at low abundance in human and mouse neuroblastoma. Knockdown HOTAIRM1 altered cell cycle progression and delayed the retinoic acid-induced dopaminergic differentiation of human SHSY5Y cells. The dopamine related genes including tyrosine hydroxylase (the rate limiting enzyme for dopamine synthesis and dopamine neuronal marker), vesicular monoamine transporter 2 and monoamine oxidase were reduced by HOTAIRM1 attenuation. Furthermore, we observed a dramatic increase in the number of caspase 3 positive cells when HOTAIRM1 was decreased, suggesting reduction of HOTAIRM1 could lead to apoptosis of human neuroblastoma. We also found that reducing HOTAIRM1 modulated DNA methylation and histone methylation, indicating that HOTAIRM1 modulate cell proliferation, differentiation and apoptosis via epigenetic pathways. Collectively, we revealed that noncoding RNA HOTAIRM1 modulates the growth and apoptosis of human and mouse neuroblastomas. This noncoding RNA could be a potential therapeutic target in the treatment of human neuroblastoma.
Mehrnaz Ajorloo
Avicenna Research center, Iran
Title: The Effect of DNA Hypomethylation in the Trend of Breast Cancer
Biography:
She is a Biotechnologist working in The society for Infertility Sciences, Avicenna Research center, Tehran, Iran. She completed her medical studies in Genetic engineering at Rudehen Azad University, Tehran, Iran. She has published more than 10 papers in reputed journals and has been serving as an editorial board member of repute.
Abstract:
Cancer is a disease that ranked first in the world and breast cancer is One of its types that can be caused by environmental and genetic factors. Therefore, more detailed studies on the effects of epigenetic factors in breast cancer Can lead to finding useful outcomes for prevention and treatment. As you know, Controlled Reversible Processes Collection that Causing genetic variations in the expression of genes And marking the gene independent of the change in the nucleotide sequence of the DNA is Epigenetic. The agents of this process alter the expression of the microRNAs in the cell either directly or indirectly and certainly Defect in these mechanisms leads to the activation or Inhibiting different messenger paths and causing cancer.
existing Hypermethylation in epigenetic mechanisms In certain promoters They can activate the expression of inappropriate oncogenes And play a role as a tumor suppressor gene in breast cells In the form of hypermethylated. In recent research, More than 100 hypermethylated genes have been identified in breast tumors with breast cancer cell lines that Most of these methylated genes play an important role in the cell cycle ،Apoptosis ، metastases and they have tissue invasion Angiogenesis and hormonal signalling. The cyclin D2 gene is an important regulator of the cell cycle And increasing its expression Harnesses the Transfer from step G1 to S in the cell cycle. This gene is often methylated in breast cancer and It is posing as the first event in the development of this cancer.
Biography:
He began his education in 2013 in medicine in Guilan University School of Medicine, Rasht-IRAN. He has published more than 10 papers in reputed journals and has been serving as an editorial board member of repute.
Abstract:
Nowadays, According to the high rate of cancer Problems and complications arising from it، Research Is doing in order to find the way to work " for the prevention، The early diagnosis and treat it. Iran, also, like in other countries, is faceing with increase in cancer rate that we can pointing to breast cancer That is the most common cancer with a high rate between women that There is a chance that someone will get this cancer From every 10 to 15 women in Iran. So studies of epigenetic is very important.
Breast cancer has more chance for Progression to tumor in case of being dependent to hormone. Different types of breast cancer are often positive estrogen receptor and positive progesterone receptor And Their growth is stimulated by these hormones And Is restrained by anti-estrogens.
DNA methylation in ESPRI and PGR promoters Has been raised As a mechanism for the spread of ER-negative tumors in cell lines And primary tumors. ER-negative breast cancer cells are Also Missing mRNA Related to estrogen receptor that it can be due to hypomethylation. It has been noted in studies that expresses the ER gene in ER-negative cells by inhibiting methylation It will be activated again that leads to the expansion of the necessary conditions for this type of cancer.