Eleni Josephides

Bio: Eleni Josephides is an academic researcher from The Queen's Medical Center. The author has contributed to research in topics: Medicine & Lung cancer. The author has an hindex of 1, co-authored 2 publications receiving 635 citations.

The molecular genetics of colorectal cancer

Abstract: Colorectal cancer is a common but heterogeneous disease, which arises through the accumulation of genetic mutations Knowledge of the molecular basis of colorectal cancer has advanced at a rapid pace in recent years, reflecting progress made in the field of genomic medicine Targeted therapies have come into mainstream use, and the exciting prospect of treatment regimens tailored to the mutation profile of individual tumours is beginning to emerge In order to understand the development and application of the next generation of colorectal cancer treatments, it is important that gastroenterologists have a working knowledge of the pathological mechanisms that drive the disease This review examines our current understanding of the molecular genetics of colorectal carcinogenesis

Enthesitis in association with inflammatory bowel disease.

Abstract: A 27-year-old Sudanese woman presented to the emergency department with a 1-week history of lumbar back pain radiating to the buttocks. There was no history of trauma, fever or weight loss. Medical history included ulcerative colitis, maintained in remission with oral mesalazine. On examination, there was midline tenderness over the upper lumbar spine. Neurological examination was normal. MRI of the lumbar spine (figure 1) demonstrated oedema in …

Comprehensive molecular characterization of human colon and rectal cancer

Abstract: To characterize somatic alterations in colorectal carcinoma, we conducted a genome-scale analysis of 276 samples, analysing exome sequence, DNA copy number, promoter methylation and messenger RNA and microRNA expression. A subset of these samples (97) underwent low-depth-of-coverage whole-genome sequencing. In total, 16% of colorectal carcinomas were found to be hypermutated: three-quarters of these had the expected high microsatellite instability, usually with hypermethylation and MLH1 silencing, and one-quarter had somatic mismatch-repair gene and polymerase e (POLE) mutations. Excluding the hypermutated cancers, colon and rectum cancers were found to have considerably similar patterns of genomic alteration. Twenty-four genes were significantly mutated, and in addition to the expected APC, TP53, SMAD4, PIK3CA and KRAS mutations, we found frequent mutations in ARID1A, SOX9 and FAM123B. Recurrent copy-number alterations include potentially drug-targetable amplifications of ERBB2 and newly discovered amplification of IGF2. Recurrent chromosomal translocations include the fusion of NAV2 and WNT pathway member TCF7L1. Integrative analyses suggest new markers for aggressive colorectal carcinoma and an important role for MYC-directed transcriptional activation and repression.

Epidemiology of colorectal cancer: incidence, mortality, survival, and risk factors

Abstract: According to GLOBOCAN 2018 data, colorectal cancer (CRC) is the third most deadly and fourth most commonly diagnosed cancer in the world. Nearly 2 million new cases and about 1 million deaths are expected in 2018. CRC incidence has been steadily rising worldwide, especially in developing countries that are adopting the "western" way of life. Obesity, sedentary lifestyle, red meat consumption, alcohol, and tobacco are considered the driving factors behind the growth of CRC. However, recent advances in early detection screenings and treatment options have reduced CRC mortality in developed nations, even in the face of growing incidence. Genetic testing and better family history documentation can enable those with a hereditary predisposition for the neoplasm to take preventive measures. Meanwhile, the general population can reduce their risk by lowering their red meat, alcohol, and tobacco consumption and raising their consumption of fibre, wholesome foods, and certain vitamins and minerals.

Recurrent R-spondin fusions in colon cancer

Abstract: Identifying and understanding changes in cancer genomes is essential for the development of targeted therapeutics1. Here we analyse systematically more than 70 pairs of primary human colon tumours by applying next-generation sequencing to characterize their exomes, transcriptomes and copy-number alterations. We have identified 36,303 protein-altering somatic changes that include several new recurrent mutations in the Wnt pathway gene TCF7L2, chromatin-remodelling genes such as TET2 and TET3 and receptor tyrosine kinases including ERBB3. Our analysis for significantly mutated cancer genes identified 23 candidates, including the cell cycle checkpoint kinase ATM. Copy-number and RNA-seq data analysis identified amplifications and corresponding overexpression of IGF2 in a subset of colon tumours. Furthermore, using RNA-seq data we identified multiple fusion transcripts including recurrent gene fusions involving R-spondin family members RSPO2 and RSPO3 that together occur in 10% of colon tumours. The RSPO fusions were mutually exclusive with APC mutations, indicating that they probably have a role in the activation of Wnt signalling and tumorigenesis. Consistent with this we show that the RSPO fusion proteins were capable of potentiating Wnt signalling. The R-spondin gene fusions and several other gene mutations identified in this study provide new potential opportunities for therapeutic intervention in colon cancer.

Modeling colorectal cancer using CRISPR-Cas9-mediated engineering of human intestinal organoids

Abstract: Genome editing applied to human intestinal organoids enables the study of the functional effects of mutations recurrent in human tumors.