Identification of hereditary breast and ovarian cancer germline variants in Granada (Spain): NGS perspective.

The aim of this study was to assess the prevalence of germline variants in cancer-predisposing genes by either targeted (BRCA1/2) or multigene NGS panel in a high-risk Hereditary Breast and Ovarian Cancer (HBOC) cohort. Samples from 824 Caucasian probands were retrospectively collected and the impact of genetic diagnosis and genetic variants epidemiology in this cohort was evaluated. Performance of risk-reducing prophylactic measures, such as prophylactic mastectomy and/or prophylactic oophorectomy, was assessed through clinical follow-up of patients with a positive genetic result. Pathogenic variants predisposing to HBOC were identified in 11.9% (98/824) individuals at BRCA2 (47/98), BRCA1 (24/98), PALB2 (8/51), ATM (7/51), CHEK2 (6/51) MSH6, (2/51), RAD51C (2/51) and TP53 (2/386). Of them, 11 novel pathogenic variants and 12 VUS were identified, characterized, and submitted to ClinVar. Regarding clinical impact, the risk of developing basal or Her2 breast cancer was increased 15.7 times or 37.5 times for BRCA1 and MSH6 pathogenic variants respectively. On the contrary, the risk of developing basal or luminal A breast cancer was reduced to 81% or 77% for BRCA2 and BRCA1 pathogenic variants, respectively. Finally, 53.2% of individuals testing positive for class IV/V variants underwent prophylactic surgery (mastectomy, oophorectomy or both) being significantly younger at the cancer diagnosis than those undertaking prophylactic measures (p = 0.008). Of them, 8 carried a pathogenic/likely pathogenic variant in other genes different from BRCA1 and BRCA2, and the remaining (46.7%) decided to continue with clinical follow-up. No differences in pathogenicity or risk of developing cancer were found for BRCA1/2 between targeted and multigene sequencing strategies; however, NGS was able to resolve a greater proportion of high-risk patients.

Genetic variation of 17 STR loci in a Mexican Mestizo population from Mexico City.

Genetic data from 17 autosomal short tandem repeat (STR) loci found in the Powerplex® ESX 17 System (Promega, Madison, WI, USA) was evaluated in 162 unrelated Mexican Mestizo individuals from Mexico City. Allele frequencies and forensic parameters were estimated for the 17 STRs. All loci analyzed were in Hardy-Weinberg equilibrium in the studied population and showed not any signs of linkage between loci. The combined power of discrimination and the power of exclusion for the 16 aSTRs studied were 1-2.56409·10-19 and 99.999938 %, respectively. Genetic distances reveal a close relationship within different populations of Mexican Mestizos. The obtained data might be useful for population genetics research and for individual identification and paternity testing in forensic science.

Searching for urine biomarkers of bladder cancer recurrence using a liquid chromatography-mass spectrometry and capillary electrophoresis-mass spectrometry metabolomics approach.

The incidence and rate of recurrence of bladder cancer is high, particularly in developed countries, however current methods for diagnosis are limited to detecting high-grade tumours using often invasive methods. A panel of biomarkers to characterise tumours of different grades that could also distinguish between patients exhibiting the disease with first incidence or recurrence could be useful for bladder cancer diagnostics. In this study, potential metabolic biomarkers have been discovered through mass spectrometry based metabolomics of urine. Pre-treatment urine samples were collected from 48 patients diagnosed of urothelial bladder cancer. Patients were followed-up through the hospital pathological charts to identify whether and when the disease recurred or progressed. Subsequently, they were classified according to whether or not they suffered a tumour recurrence (recurrent or stable) as well as their risk group according to tumour grade and stage. Identified metabolites have been analysed in terms of disease characteristics (tumour stage and recurrence) and have provided an insight into bladder cancer progression. Using both liquid chromatography and capillary electrophoresis-mass spectrometry, a total of 27 metabolite features were highlighted as significantly different between patient groups. Some, for example histidine, phenylalanine, tyrosine and tryptophan have been previously linked with bladder cancer, however until now their connection with bladder cancer progression has not been previously reported. The candidate biomarkers revealed in this study could be useful in the clinic for diagnosis of bladder cancer and, through characterising the stage of the disease, could also be useful in prognostics.

Circulating tumour cells in peripheral blood: potential impact on breast cancer outcome.

INTRODUCTION: In breast cancer, the metastatic process may involve the dissemination of circulating tumour cells (CTCs) through the blood and lymphatic system prior to the colonisation of distant organs. Here we demonstrate the predictive capacity of CTCs for detecting risk of death in breast cancer patients during established time intervals. METHODS: CTCs were identified by immunocytochemical methods following isolation by selective immunomagnetic cell separation of cytokeratin-positive cells. Serial blood samples from 65 patients were collected at roughly monthly intervals for up to 50 months. Follow-up was conducted at different intervals: 1-5, >5-12, >12-24 and >24-50 months. RESULTS: Both presence and number of CTCs were correlated to risk of death: patients with CTCs at any time during follow-up had a higher risk of death (p=0.035) than patients without CTCs. Furthermore, during the first 5 months of therapy, patients with >5 CTCs had a higher risk of death than patients with <5 CTCs (p=0.002). CONCLUSIONS: Our results show that the persistence of CTCs after chemotherapy, particularly during the first 5 months, could define a group of patients with a high risk of relapse.