This is the first study performed in Murcia (south-eastern Spain) in which 592 families with hereditary breast and ovarian cancer were identified thanks to Genetic Counselling Units from this area over 6 years. Diagnostic performance was 18.1% and 194 different genetic variants were obtained. Variants with uncertain significance accounted for only 5.6% of the total number of reports, so our population has been well characterised. In BRCA1 gene, two novel variants were found (c.1859delT and c.3205C > T) and the most frequently detected mutations were c.68_69delAG, c.212 + 1G > A, c.5123C > A, c.211A > G and c.1918C > T, which together represented 56.67% of total pathogenic mutations. In BRCA2 gene, four recurrent variants were described (deletion of entire exon 2, c.9117G > A, c.3264dupT and c.3455T > G) representing 43.5% of the mutations in this gene. Mutation c.68_69delAG and deletion of entire exon 2 in BRCA1 and BRCA2 genes respectively were the most prevalent variants in our population. Regarding the genotype-phenotype relation, mutation c.212 + 1G > A appeared in an important percentage of breast and ovarian cancer cases, c.5123C > A in bilateral breast cancer and c.9117G > A in bilateral breast cancer and ovarian cancer. With respect to clinical-pathological characteristic, BRCA1/BRCA2 mutation carriers showed earlier onset age of breast tumour and higher risk of developing contra lateral breast cancer than non-informative cases. Moreover, association between either molecular subtype triple negative breast cancer or ovarian cancer and BRCA1 carriers was obtained.

Gastric cancer (GC) is one of the leading causes of cancer-related death. The combination of new molecular classifications with clinicopathological data could contribute to the individualization of patients and to the development of new therapeutic strategies. We examined the various associations in two molecular types of GC: HER2-positive (human epidermal growth factor receptor 2) and microsatellite instability (MSI), assessing their influence on treatment and prognosis. A retrospective study of 142 GC patients was performed with molecular characterization through HER2 overexpression and DNA repair protein expression for MSI. The percentage of HER2-positive tumors was 13.4%, predominantly in men. Correlations were found with intestinal type, metastases, advanced stages and chemotherapy. Almost 75% of HER2-positive patients died. MSI occurred in 16.2%, associated with advanced age, female sex, distal location and intestinal type. These patients had few metastases and low stages. The percentage of deaths was higher among MSI patients who received perioperative chemotherapy. The determination of HER2 and MSI status in GC is important for their association with specific clinicopathological features and for their prognostic and predictive value.

Adult onset hemophagocytic lymphohistiocytosis (HLH) is a rare condition, usually secondary to either a precipitating infective or hematologic malignancy. We present a case of Epstein–Barr virus associated HLH in a 55-year-old female receiving treatment for a glioblastoma (GBM). It is possible that HLH is under recognized, as patients with GBM often have features of a nonspecific systemic inflammatory response syndrome, multiorgan failure and cognitive decline. A high index of suspicion and increased awareness can help improve timeliness of diagnosis. Therapeutically, Epstein–Barr virus associated HLH in patients with solid organ malignancy poses significant challenges. An individualized, multidisciplinary approach is essential when managing adult-onset HLH and providers will need to be mindful of the high mortality rate despite treatment.

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Mutations in breast cancer susceptibility (BRCA) genes lead to defects in DNA repair processes resulting in elevated genome instability and predisposing to breast and ovarian cancer. We report a novel mutation (c.1918C>T) in the exon 11 of the BRCA1 gene that consists of a nonsense mutation that causes a stop codon downstream in the 640 position of the protein. The mutation was present in two Spanish unrelated families and was associated with four breast cancer cases, including two bilateral breast cancer (one of them synchronous). The median age/mean age (range) was 48.5/44.25 years (27-53). This finding led us to perform haplotype analysis in all family carriers. Four highly polymorphic microsatellite markers were used (17-3858, 17-3930, D17S855, D17S1326) to establish whether or not all these families had a common ancestor. This analysis showed that all mutation carriers of these families had a common haplotype. None of the noncarriers of the mutation or of the 24 healthy controls showed this haplotype. Therefore, the c.1918C>T mutation carriers from these two families allows us to assert that all analyzed mutation carriers share a common ancestry.

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