Background Hereditary cancer predisposition syndromes are responsible for approximately 5–10% of all diagnosed cancer cases. In the past, single-gene analysis of specific high risk genes was used for the determination of the genetic cause of cancer heritability in certain families. The application of Next Generation Sequencing (NGS) technology has facilitated multigene panel analysis and is widely used in clinical practice, for the identification of individuals with cancer predisposing gene variants. The purpose of this study was to investigate the extent and nature of variants in genes implicated in hereditary cancer predisposition in individuals referred for testing in our laboratory. Methods In total, 1197 individuals from Greece, Romania and Turkey were referred to our laboratory for genetic testing in the past 4 years. The majority of referrals included individuals with personal of family history of breast and/or ovarian cancer. The analysis of genes involved in hereditary cancer predisposition was performed using a NGS approach. Genomic DNA was enriched for targeted regions of 36 genes and sequencing was carried out using the Illumina NGS technology. The presence of large genomic rearrangements (LGRs) was investigated by computational analysis and Multiplex Ligation-dependent Probe Amplification (MLPA). Results A pathogenic variant was identified in 264 of 1197 individuals (22.1%) analyzed while a variant of uncertain significance (VUS) was identified in 34.8% of cases. Clinically significant variants were identified in 29 of the 36 genes analyzed. Concerning the mutation distribution among individuals with positive findings, 43.6% were located in the BRCA1/2 genes whereas 21.6, 19.9, and 15.0% in other high, moderate and low risk genes respectively. Notably, 25 of the 264 positive individuals (9.5%) carried clinically significant variants in two different genes and 6.1% had a LGR. Conclusions In our cohort, analysis of all the genes in the panel allowed the identification of 4.3 and 8.1% additional pathogenic variants in other high or moderate/low risk genes, respectively, enabling personalized management decisions for these individuals and supporting the clinical significance of multigene panel analysis in hereditary cancer predisposition. Electronic supplementary material The online version of this article (10.1186/s12885-019-5756-4) contains supplementary material, which is available to authorized users.

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ObjectivesTreatment decision-making in colorectal cancer is often guided by tumour tissue molecular analysis. The aim of this study was the development and validation of a high-resolution melting (HRM) method for the detection of KRAS, NRAS and BRAF mutations in Greek and Romanian patients with colorectal cancer and determination of the frequency of these mutations in the respective populations.SettingDiagnostic molecular laboratory located in Athens, Greece.Participants2425 patients with colorectal cancer participated in the study.Primary and secondary outcome measures2071 patients with colorectal cancer (1699 of Greek and 372 of Romanian origin) were analysed for KRAS exon 2 mutations. In addition, 354 tumours from consecutive patients (196 Greek and 161 Romanian) were subjected to full KRAS (exons 2, 3 and 4), NRAS (exons 2, 3 and 4) and BRAF (exon 15) analysis. KRAS, NRAS and BRAF mutation detection was performed by a newly designed HRM analysis protocol, followed by Sanger sequencing.ResultsKRAS exon 2 mutations (codons 12/13) were detected in 702 of the 1699 Greek patients with colorectal carcinoma analysed (41.3%) and in 39.2% (146/372) of the Romanian patients. Among the 354 patients who were subjected to full KRAS, NRAS and BRAF analysis, 40.96% had KRAS exon 2 mutations (codons 12/13). Among the KRAS exon 2 wild-type patients 15.31% harboured additional RAS mutations and 12.44% BRAF mutations. The newly designed HRM method used showed a higher sensitivity compared with the sequencing method.ConclusionsThe HRM method developed was shown to be a reliable method for KRAS, NRAS and BRAF mutation detection. Furthermore, no difference in the mutation frequency of KRAS, NRAS and BRAF was observed between Greek and Romanian patients with colorectal cancer.

Aim: To evaluate the effectiveness of a biosimilar erythropoiesis-stimulating agent (Binocrit®) for the treatment of patients with cancer and chemotherapy-induced anemia in real-life clinical practice. Materials & methods: Data were collected retrospectively from patients at five European centers (in France, Italy, The Netherlands, Romania and Spain) who received treatment with Binocrit. Hemoglobin (Hb) levels were recorded at regular intervals during Binocrit therapy for up to 26 weeks. Hb response (an increase of ≥1 g/dl in 4 weeks or a Hb level in the range 10–12 g/dl during the study) was assessed in patients with a Hb level ≥8.5 g/dl at the start of therapy who received treatment for at least 6 weeks. Hb response rates in patients who did and did not receive intravenous (iv.) iron were also assessed, and data on any serious unexpected adverse events were collected. Results: Among evaluable patients (n = 113), 79% achieved a Hb response. Response rates were similar among evaluable patients who received an initial Binocrit dose of 30,000 or 40,000 IU/week (81 vs 78%; p = not significant). The Hb response rate was significantly greater in patients who received iv. iron than in patients who did not receive iv. iron (93 vs 77%; p < 0.05). No serious unexpected adverse events were reported. Conclusion: Use of the biosimilar erythropoiesis-stimulating agent Binocrit is effective and safe for the treatment of patients with cancer and chemotherapy-induced anemia. Supplementation with iv. iron increases the response rate compared with oral or no iron supplementation.