Reduced BRCA1 expression due to promoter hypermethylation in therapy-related acute myeloid leukaemia

BRCA1 plays a pivotal role in the repair of DNA damage, especially following chemotherapy and ionising radiation. We were interested in the regulation of BRCA1 expression in acute myeloid leukaemia (AML), in particular in therapy-related forms (t-AML). Using real-time PCR and Western blot, we found that BRCA1 mRNA was expressed at barely detectable levels by normal peripheral blood granulocytes, monocytes and lymphocytes, whereas control BM-mononuclear cells and selected CD34+ progenitor cells displayed significantly higher BRCA1 expression (P=0.0003). Acute myeloid leukaemia samples showed heterogeneous BRCA1 mRNA levels, which were lower than those of normal bone marrows (P=0.0001). We found a high frequency of hypermethylation of the BRCA1 promoter region in AML (51/133 samples, 38%), in particular in patients with karyotypic aberrations (P=0.026), and in t-AML, as compared to de novo AML (76 vs 31%, P=0.0002). Examining eight primary tumour samples from hypermethylated t-AML patients, BRCA1 was hypermethylated in three of four breast cancer samples, whereas it was unmethylated in the other four tumours. BRCA1 hypermethylation correlated to reduced BRCA1 mRNA (P=0.0004), and to increased DNA methyltransferase DNMT3A (P=0.003) expression. Our data show that reduced BRCA1 expression owing to promoter hypermethylation is frequent in t-AML and that this could contribute to secondary leukaemogenesis

Mutation spectrum of MLL2 in a cohort of kabuki syndrome patients

ABSTRACT: BACKGROUND: Kabuki syndrome (Niikawa-Kuroki syndrome) is a rare, multiple congenital anomalies/mental retardation syndrome characterized by a peculiar face, short stature, skeletal, visceral and dermatoglyphic abnormalities, cardiac anomalies, and immunological defects. Recently mutations in the histone methyl transferase MLL2 gene have been identified as its underlying cause. METHODS: Genomic DNAs were extracted from 62 index patients clinically diagnosed as affected by Kabuki syndrome. Sanger sequencing was performed to analyze the whole coding region of the MLL2 gene including intron-exon junctions. The putative causal and possible functional effect of each nucleotide variant identified was estimated by in silico prediction tools. RESULTS: We identified 45 patients with MLL2 nucleotide variants. 38 out of the 42 variants were never described before. Consistently with previous reports, the majority are nonsense or frameshift mutations predicted to generate a truncated polypeptide. We also identified 3 indel, 7 missense and 3 splice site. CONCLUSIONS: This study emphasizes the relevance of mutational screening of the MLL2 gene among patients diagnosed with Kabuki syndrome. The identification of a large spectrum of MLL2 mutations possibly offers the opportunity to improve the actual knowledge on the clinical basis of this multiple congenital anomalies/mental retardation syndrome, design functional studies to understand the molecular mechanisms underlying this disease, establish genotype-phenotype correlations and improve clinical management

Relationships between woody vegetation and geomorphological patterns in three gravel-bed rivers with different intensities of anthropogenic disturbance

We compared three gravel-bed rivers in north-eastern Italy (Brenta, Piave, Tagliamento) having similar bioclimate, geology and fluvial morphology, but affected by different intensities of anthropogenic disturbance related particularly to hydropower dams, training works and instream gravel mining. Our aim was to test whether a corresponding difference in the interactions between vegetation and geomorphological patterns existed among the three rivers. In equally spaced and sized plots (n = 710) we collected descriptors of geomorphic conditions, and presence-absence of woody species. In the less disturbed river (Tagliamento), spatial succession of woody communities from the floodplain to the channel followed a profile where higher elevation floodplains featured more developed tree communities, and lower elevation islands and bars were covered by pioneer communities. In the intermediate-disturbed river (Piave), islands and floodplains lay at similar elevation and both showed species indicators of mature developed communities. In the most disturbed river (Brenta), all these patterns were simplified, all geomorphic units lay at similar elevations, were not well characterized by species composition, and presented similar persistence age. This indicates that in human-disturbed rivers, channel and vegetation adjustments are closely linked in the long term, and suggests that intermediate levels of anthropogenic disturbance, such as those encountered in the Piave River, could counteract the natural, more dynamic conditions that may periodically fragment vegetated landscapes in natural rivers. © 2015 Elsevier Ltd

Analisi spaziale numerica dei mesohabitat fluviali: medio corso del fiume Panaro (MO)

Il fiume Panaro presenta notevoli criticit\ue0 dovute allo sfruttamento antropico. Questo studio presenta una metodologia speditiva, sulla base di ortofoto ad alta risoluzione e rilievi di campo sulla vegetazione, per individuare e cartografare i mesohabitat fluviali, analizzarne la qualit\ue0 e diversit\ue0 e per evidenziare gli impatti delle opere di artificializzazione

Analisi spaziale numerica dei mesohabitat fluviali: medio corso del fiume Panaro(MO)

Il Fiume Panaro presenta notevoli criticit\ue0 correlate allo sfruttamento antropico del territorio. Questo studio si pone di analizzare lo stato e la quantit\ue0 dei mesohabitat a disposizione per le comunit\ue0 fluviali utilizzando le ortofoto Quickbird 2003 ad alta risoluzione. Il processo di fotointerpretazione delle ortofoto, condotto alla scala di 1:3000, permette di caratterizzare differenti habitat. con il controllo di sopralluoghi mirati in campo. La successiva digitalizzazione degli habitat fornisce i dati per effettuare stime numeriche in modo speditivo, al fine di evidenziare le relazioni spaziali tra le artificializzazioni rilevate e la conseguente banalizzazione degli ambienti fluvial