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included in this spectrum: isolated lymphatic malformations (OMIM disease not available), congenital lipomatous overgrowth, vascular malformations and epidermal nevi syndrome (CLOVES, OMIM disease 612918), Klippel-Trenaunay syndrome (KTS, OMIM disease 149000) and fibro-adipose vascular anomaly (FAVA, OMIM disease not available) ( 34 ); Proteus syndrome (OMIM disease 176920) caused by somatic mutations in AKT1 (OMIM gene 164730) ( 35 ). Other likely genes ADM (OMIM gene 103275) , CALCRL (OMIM gene 114190) , CDH5 (OMIM gene 601120) , PDPN (OMIM gene 608863) , RAMP2

). When more than one type of vessel is affected, the term mixed anomaly is used. Vascular anomalies can also occur in the context of syndromes ( 2 ). Disorders characterized by VAs have phenotypic variability within the same entity, overlapping clinical features between different conditions, allelic and locus heterogeneity, and the same disorder can be inherited in different ways. Although most vascular anomalies are sporadic (paradominant inheritance or de novo somatic mutations), there are well-described syndromic and hereditary forms of VAs (autosomal dominant

submicroscopic alterations in the genes involved in tumor suppression, apoptosis, and cell-cycle regulation, contributing to more comprehensive insight into leukemogenesis. And not only that, these new markers have been used in diagnosis, risk-stratification and targeted therapy application, leading to improvement of current protocols and patient management ( 6 , 7 ). In this study, we applied targeted next generation sequencing on MiSeq System for analyzing somatic mutations in groups of adult (aALL) and childhood (cALL) ALL patients, in order to facilitate recognition and

same patient. 3 After that, from the number of possible somatic mutations, only a handfull of genes were recurrently mutated in multiple AML genomes, including mutations in the genes for isocitrate dehydrogenase 1 ( IDH1 ) and isocitrate dehydrogenase 2 ( IDH2 ). The IDH1 and IDH2 genes, located at chromosome bands 2q33.3 and 15q26.1 respectively, encode NADPH (reduced nicotinamide adenine dinucleotide phosphate) - dependent isocitrate dehydrogenase 1/2 enzymes, whose main role is to protect cells from oxidative stress. 4 Heterozygous point mutations in IDH1

Abstract

Detection of mutations in cancer is particularly important in terms of proper treatment and targeted therapy. The aim of this study was the comparison of two methods: allele-specific PCR (AS-PCR) and dideoxysequencing applied for the identification of BRAF gene mutations in wild-type gastrointestinal stromal tumors (WT GISTs). We have optimized the conditions for the detection V600E mutation representing the c.1799 T>A substitution by AS-PCR and have used dideoxysequencing to verify our results. In nine cases, we were able to detect the mutation by AS-PCR approach; however, the mutations have been confirmed by dideoxysequencing in four cases only. AS-PCR is fast and low cost method for the detection of V600E mutation which was validated as a sensitive assay for the identification of the most common BRAF mutation in DNA extracted from paraffin-embedded tissue of WT GISTs.

Summary

Background: Genetic studies of salivary gland neoplasms were mainly focused on chromosomal changes, and some specific patterns of chromosome translocations have been described. However, molecular alterations, in particular the role of HER-2/H-ras/c-myc signalling cascade in pleomor- phic adenoma pathogenesis (PA), are less well characterized. In addition, data on single nucleotide polymorphisms (SNPs) as potential susceptibility factors for PA development are also quite scarce.

Methods: Mutational analyses were performed by means of real-time PCR (HER-2 and c-myc amplification analysis), PCR-SSCP and sequencing (H-ras point mutation detec- tion). Polymorphisms analysis was performed by PCR-RFLP (survivin and MMP-9 genes).

Results: Amplification of HER-2 and c-myc has been found in 13% and 9% of PA cases respectively. Point mutations in H-ras codons 12/13 have been detected in 17% of PAs. No correlation could be established between these alterations and clinical characteristics of PAs, whereas they might play a role in a subset of malignant salivary gland tumours. As for survivin -31 G/C polymorphism, C allele carriers had a 4-fold decrease of the risk of developing PA (p=0.05). Carriers of the variant allele T of the -1562C/T SNP in MMP-9 gene had a 4-fold increase of the risk of developing PA (p<0.001).

Conclusions: A longer follow-up of PA patients harbouring mutations could uncover a prognostic role of HER-2 and c- myc amplification as predictors of adenoma transformation into carcinoma. Both survivin and MMP-9 promoter poly- morphisms represent susceptibility factors for the develop- ment of PAs in the Serbian population.

are not only associated with germline mutations (affecting all cells of the body and potentially transmissible to offspring) but also with somatic mutations (specific to affected tissue and not transmissible to offspring) ( 1 , 2 ). In some cases, a somatic mutation in affected tissue and a germline variant are necessary for the defect to manifest (second-hit mechanism) ( 3 , 4 ). Molecular biology has enabled researchers to classify cardiovascular defects on the basis of their molecular etiology. Understanding the molecular causes of these disorders has permitted

from FFPE NSCLC samples from primary tumors by QIAamp DNA FFPE Tissue Kit (Qiagen Ltd.) for genomic DNA purification. The concentrations of the DNA samples were measured by NanoDrop Lite spectrophotometer system (Thermo Fisher Scientific, Waltham, MA, USA). The therascreen EGFR RGQ PCR Kit (Qiagen Ltd.) was custom-made for detecting 29 somatic mutations in exons 18-21 of the EGFR gene using a RT-PCR technology. The amplification reaction was done on the Rotor-Gene Q instrument (Qiagen Ltd.). For detecting the mutations with RT-PCR, the assay used two technologies

registered in children with polymorphic CM ( 33 , 34 ). KIT D816V mutation is found in most patients with ISM (>90%), who are characterized by favorable prognosis ( 35 , 36 ). This leads to a conclusion that there are other non-D816V KIT mutations, contributing to the pathogenesis and determining aggressive course of the disease ( 32 , 37 ). In fact, several other somatic mutations in TET2, SRSF2, ASXL1, CBL, RUNX1 and RAS in patients with SM-AHN, ASM, MCL were detected ( 5 , 24 ). Non-KIT mutations in SM-AHN are found not only in MCs, but also in other myeloid cells

Research on Cancer 2008 2 Rumi E, Pietra D, Pascutto C, Guglielmelli P, Martinez-Trillos A, Casetti I, et al. Clinical effect of driver mutations of JAK2, CALR, or MPL in primary myelofibrosis. Blood. 2014; 124(7): 1062-1069. 10.1182/blood-2014-05-578435 Rumi E Pietra D Pascutto C Guglielmelli P Martinez-Trillos A Casetti I et al Clinical effect of driver mutations of JAK2, CALR, or MPL in primary myelofibrosis Blood 2014 124 7 1062 1069 3 Klampfl T, Gisslinger H, Harutyunyan AS, Nivarthi H, Rumi E, Milosevic JD, et al. Somatic mutations of calreticulin in