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Elias A. Kotteas and Konstantinos N. Syrigos

the changes in tumor vascularity and the patient’s pre- and post-treatment immunity, detection of immune biomarkers to measure antiangiogenic responses is essential. Furthermore, the optimal doses and the schedule of treatment modalities should be determined to achieve clinical effectiveness and to avoid serious side effects. Next-generation sequencing, which encompasses whole genome, whole transcriptome sequencing, whole exome, and targeted sequencing, has substantially expanded our knowledge in cancer biology by identifying mutations with high sensitivity and

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George Fotopoulos, Ioannis Vathiotis, George C. Nikou and Konstantinos Syrigos

element in tumorigenesis and dissemination. It also exhibits a potential substrate-dependent antiangiogenic potential [11] . Such alterations have been found in various NETs specimens so it seems that there is some implication of this gene in the pathogenesis. TP53 gene, situated in the short arm of chromosome 17, represents the most frequently mutated gene (>50%) in malignant tumors, indicating its pivotal role in carcinogenesis. TP53 gene encodes proteins that bind to DNA and adjust gene expression to prevent mutations of the genome [12] . If the TP53 gene is

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Alexios Matikas, Georgios Lazaridis and Sofa Agelaki

2011;121:2750−67. [41] Parker JS, Mullins M, Cheang MC et al. Supervised risk predictor of breast cancer based on intrinsic subtypes. J Clin Oncol. 2009;27:1160-7. [42] Lehmann BD, Pietenpol JA. Identification and use of biomarkers in treatment strategies for triple-negative breast cancer subtypes. J Pathol 2014;232:142-50. [43] Cancer Genome Atlas Network. Comprehensive molecular portraits of human breast tumours. Nature 2012;490:61−70. [44] Marty B, Maire V, Gravier E et al. Frequent PTEN genomic alterations and activated phosphatidylinositol 3-kinase

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Georgios Lypas

satisfaction about their tests [ 38 ]. This result is rather surprising, contrasting relevant guidelines. It is the author’s opinion that for many countries, effort and resources should be primarily allocated to the proper adoption of testing and management guidelines, until at least the proportion of women who get tested corresponds to the vast majority of those who fulfill testing criteria, and their further management is according to these guidelines. References [1] Stadler, Z.K., et al., Genome-wide association studies of cancer . J Clin Oncol, 2010. 28(27): p

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E. Veniou, I. Sofatzis, I. Kalantzis, M. Karakosta, M. Logothetis, E. Lianos and N. Ziras

Center for Health Statistics, which is part of the CDC, NCI is supporting the use of activity monitors to collect objective physical activity, sleep, and strength data for NHANES. Genes, Environment and Health Initiative (GEI) This trans-NIH includes an NCI-led component that invests in new technology to measure environmental toxins, dietary intake, and physical activity and to determine an individual’s biological response to those influences on the level of the genome, the proteome, and the metabolome. Measures Registry Catalogue of Surveillance

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number of somatic mutations that exist within a tumor’s genome as usually determined by Whole Exome Sequencing (WES). Measurements of TMB (Mutations per megabase (Muts/MB)) from comprehensive gene panels are strongly reflective of measurements from WES and provide a feasible, cost- and time- effective approach in clinical practice. A subset of these mutations may result in an expressed protein, termed neoantigen that is not recognized by the host’s immune system as self, and therefore has the potential to be immunogenic, leading to an antitumor immune-mediated response

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Ivana Vrhovac and Goran Nikšić

-27. Vergnaud G, Denoeud F. Minisatellites, mutability and genome architecture. Genome Res 2000; 10: 899-907. Little JB. Radiation carcinogenesis. Carcinogenesis 2000; 21: 397-404. Dubrova YE, Plumb M, Brown J, Fennely J, Bois P, Goodhead D, et al. Stage specificity, dose response and doubling dose for mouse minisatellite germline mutation induced by acute radiation. Proc Natl Acad Sci 1998; 95: 6251-5. Bois PR. Hypermutable minisatellites, a human affair. Genomics 2003; 81: 349

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Petra Hudler, Nina Kocevar Britovsek, Snjezana Frkovic Grazio and Radovan Komel

their effect in the context of polymorphic biological sequences on protein binding motifs. We used web-based software PROMO, which is part of the ALGGENE web-server. 32 , 33 The search for putative binding sites was performed using the following parameters: human species, all motifs, and all factors. The data for comparisons of genotype frequencies in European populations of examined SNPs in this study was extracted from the 1000 Genomes Project data platform using a specific version of the Ensembl browser ( ). 34 Results

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Matej Horvat and Borut Stabuc

Microsatellite instability in colorectal cancer

Background. Colorectal cancer (CRC) is the third most common cancer in the world. In 75% CRC develops sporadically, in 25% hereditary or as a consequence of inflammatory bowel disease. CRC carcinogenesis develops over many years. The cause of CRC in 85% is chromosomal instability (CIN) and in 15% microsatellite instability (MSI-H), where hereditary nonpolyposis colorectal cancer (HNPCC) represents 10-20%. Microsatellite sequences (MS) are repeated sequences of short stretches of DNA all over the genome. Microsatellite stability (MSS) means MS are the same in each cell of an individual, whereas microsatellite instability (MSI-H) means MS differ in normal and cancer cells of an individual. The cause of MSI-H is a damaged mismatch repair mechanism (MMR), with the most important MMR proteins being MSH2, MLH1 and MSH6.

Conclusions. MSI-H seems to be an important prognostic factor in CRC and an important predictive factor of CRC chemotherapeutic treatment efficacy. Clinical trials conducted until now have shown contradictory findings in different chemotherapeutic settings, adjuvant and palliative; therefore MSI-H is going to be the object of the future research. The future of cancer treatment is in the individualized therapy based on molecular characteristics of the tumour, such as MSI-H in CRC.

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Nina Hauptman and Damjan Glavac

, Drenkow J, Cheng J, Long J, Helt G, Dike S, et al. Examples of the complex architecture of the human transcriptome revealed by RACE and high-density tiling arrays . Genome Res 2005; 15: 987-97. 6. Sana J, Faltejskova P, Svoboda M, Slaby O. Novel classes of non-coding RNAs and cancer . J Transl Med 2012; 10: 103. 7. Zen K, Zhang CY. Circulating MicroRNAs: a novel class of biomarkers to diagnose and monitor human cancers . Med Res Rev 2012; 32: 326-48. 8. Taft RJ, Pang KC, Mercer TR, Dinger M, Mattick JS. Non