Network-Guided Analysis of Genes with Altered Somatic Copy Number and Gene Expression Reveals Pathways Commonly Perturbed in Metastatic Melanoma

Cancer genomes frequently contain somatic copy number alterations (SCNA) that can significantly perturb the expression level of affected genes and thus disrupt pathways controlling normal growth. In melanoma, many studies have focussed on the copy number and gene expression levels of the BRAF, PTEN and MITF genes, but little has been done to identify new genes using these parameters at the genome-wide scale. Using karyotyping, SNP and CGH arrays, and RNA-seq, we have identified SCNA affecting gene expression (‘SCNA-genes’) in seven human metastatic melanoma cell lines. We showed that the combination of these techniques is useful to identify candidate genes potentially involved in tumorigenesis. Since few of these alterations were recurrent across our samples, we used a protein network-guided approach to determine whether any pathways were enriched in SCNA-genes in one or more samples. From this unbiased genome-wide analysis, we identified 28 significantly enriched pathway modules. Comparison with two large, independent melanoma SCNA datasets showed less than 10% overlap at the individual gene level, but network-guided analysis revealed 66% shared pathways, including all but three of the pathways identified in our data. Frequently altered pathways included WNT, cadherin signalling, angiogenesis and melanogenesis. Additionally, our results emphasize the potential of the EPHA3 and FRS2 gene products, involved in angiogenesis and migration, as possible therapeutic targets in melanoma. Our study demonstrates the utility of network-guided approaches, for both large and small datasets, to identify pathways recurrently perturbed in cancer

A rare case of seronegative neurobrucellosis

Neurobrucellosis is one of the complications of brucellosis. We report a rare case of a 17-year-old girl with seronegative neurobrucellosis and depression and diplopia. Results of agglutination tests for Brucella both in serum and CSF were negative. Diagnosis was made only by positive culture of Brucella mellitensis with inoculation of the patient’s cerebrospinal fluid in a BACTEC 9050 System. The patient was successfully treated using ceftriaxone, doxycycline and rifampicin therapy for six months

A Case of HIV Infection with Thrombocytopenia: Assosiation of HIV, Thrombotic Thrombocytopenic Purpura and Brucellosis

To report a case of HIV infection presenting with thrombotic thrombocytopenic purpura (TTP) and brucellosis that responded well to plasmapheresis and anti-infective therapy. A 64-year-old woman with moderate confusion, fever and pancytopenia was admitted. HIV infection history was taken from her family and she was not receiving antiretroviral therapy last one year. She had generalized purpuric skin lesions. Wright tube agglutination test was found positive with a 1:160 dilution and the patient was diagnosed as brucellosis. Detailed literature search showed brucellosis as a possible cause of TTP. Patient was treated by plasma exchange/fresh frozen plasma and antimicrobials and the response was excellent. Although brucellosis seems to explain the clinical picture of this patient, it is revealed that broad differential diagnosis is needed to reach uncommon diagnosis like TTP particularly in HIV infected patients

Cranial imaging findings in neurobrucellosis: results of Istanbul-3 study

Objective Neuroimaging abnormalities in central nervous system (CNS) brucellosis are not well documented. The purpose of this study was to evaluate the prevalence of imaging abnormalities in neurobrucellosis and to identify factors associated with leptomeningeal and basal enhancement, which frequently results in unfavorable outcomes