Pharmacogenomic profiling of the PI3K/PTEN pathway in sporadic breast cancer

Pharmacogenomics is the study of genetic variations among individuals to predict the probability that a patient will respond to single or multidrug chemotherapy. Breast cancer is one of the most common cancers among women worldwide. Treatment of breast cancer by application of biological rationales gives us the ability to match the correct pharmacology to individual tumour genetic profiles. The breast cancers exhibit multiple anomalies in phosphatidylinositol 3 kinase pathways, such as phosphatase and tensin homolog deleted on chromosome TEN loss that can be put in context of therapy with rapamycin analogues. Considering the high incidence of breast cancer in Iran, the potential role of tumor suppressor PTEN/MMAC1gene was investigated in Isfahanian breast cancer patients. In this study, PTEN was evaluated by means of polymerase chain reaction, single strand conformation polymorphism, Heteroduplex mobility assay and direct DNA sequencing in 72 breast cancer tumors for detection and characterization of mutations. According to the results of this research, nucleotide substitutions were found in 5/72 [7%] of samples. The sporadic breast cancer patient was found to be heterozygote for the p.D92N, p.C105W, p.D107N, p.A121P and p.R 130Q mutations. One novel mutation, p.D107N, was found in this study. Loss of PTEN function in breast cancer can occur either by mutation or reduction of PTEN expression in almost half of sporadic breast tumors. This rate of mutations is an important consideration for novel therapeutic in which biological efficacy is influenced by the activity of PTEN

Molecular characterization of peroxisome biogenesis disorders with Zellweger syndrome spectrum

Peroxisome biogenesis disorders, Zellweger syndrome spectrum [PBD, ZSS] are constituted of three different phenotypically disorders: Zellweger syndrome [ZS], the most severe; neonatal adrenoleuko-dystrophy [NALD]; and infantile refsum disease [IRD], the least severe, that have been originally described based on their biochemical and molecular bases of these disorders which had been fully determined. Individuals with PBD, ZSS usually come to clinical attention in the newborn period or later in childhood. The diagnosis of PBD, ZSS can be definitively determined by biochemical assays, Measurement of plasma very-long-chain fatty acid [VLCFA] levels is the most commonly used and most informative initial screen. Mutations in thirteen different PEX genes - those that encode peroxins, the proteins required for normal peroxisome assembly - have been identified in PBD, ZSS. Mutations in PEX1, the most common cause of PBD, ZSS, are observed in about 68% of affected individuals. Sequence analysis is available clinically for the following seven genes: PEX1, PXMP3 [PEX2], PRXR1 [PEX5], PEX6, PEX10, PEX12, and PEX26