Summary. Background: Accurate estimates of the incidence of thrombotic thrombocytopenic purpura (TTP) are important to assess the resources required for current treatments as well as to anticipate the need to develop new treatments. Previous estimates have been indirect and have not reported data on patients with ADAMTS‐13 deficiency. Objective: To determine the incidence of patients with TTP‐hemolytic uremic syndrome (HUS) in three categories: all patients with clinically suspected TTP‐HUS, patients with idiopathic TTP‐HUS, and patients with severe ADAMTS‐13 deficiency. Methods: Incidence rates were estimated from the Oklahoma TTP‐HUS Registry, analyzing all 206 consecutive patients from January 1, 1996 to June 30, 2004 who were treated with plasma exchange for their initial episode of clinically suspected TTP‐HUS. ADAMTS‐13 activity was measured in 186 (90%) of the 206 patients. Results: The age–sex–race standardized annual incidence rates were 11.29 × 106 (95% CI: 9.70–12.88) for all patients with clinically suspected TTP‐HUS; 4.46 × 106 (95% CI: 3.43–5.50) for patients with idiopathic TTP‐HUS; and 1.74 × 106 (95% CI: 1.06–2.41) for patients with severe ADAMTS‐13 deficiency (<5% activity). In all three categories, the incidence rates were greater for women and for blacks. For patients with severe ADAMTS‐13 deficiency, the age–sex standardized incidence rate ratio of blacks to non‐blacks was 9.29 (95% CI: 4.33–19.93). Conclusions: Accurate incidence rate estimates for all patients with clinically suspected TTP‐HUS, idiopathic TTP‐HUS, and TTP associated with severe ADAMTS‐13 deficiency have been determined. The greater incidence among women and blacks is comparable with their increased risk for other autoimmune disorders.
Ovarian cancer is a disease characterised by complex genomic rearrangements but the majority of the genes that are the target of these alterations remain unidentified. Cataloguing these target genes will provide useful insights into the disease etiology and may provide an opportunity to develop novel diagnostic and therapeutic interventions. High resolution genome wide copy number and matching expression data from 68 primary epithelial ovarian carcinomas of various histotypes was integrated to identify genes in regions of most frequent amplification with the strongest correlation with expression and copy number. Regions on chromosomes 3, 7, 8, and 20 were most frequently increased in copy number (>40% of samples). Within these regions, 703/1370 (51%) unique gene expression probesets were differentially expressed when samples with gain were compared to samples without gain. 30% of these differentially expressed probesets also showed a strong positive correlation (r≥0.6) between expression and copy number. We also identified 21 regions of high amplitude copy number gain, in which 32 known protein coding genes showed a strong positive correlation between expression and copy number. Overall, our data validates previously known ovarian cancer genes, such as ERBB2, and also identified novel potential drivers such as MYNN, PUF60 and TPX2.
Ovarian cancer is a heterogeneous disease displaying complex genomic alterations, and consequently, it has been difficult to determine the most relevant copy number alterations with the scale of studies to date. We obtained genome-wide copy number alteration (CNA) data from four different SNP array platforms, with a final data set of 398 ovarian tumours, mostly of the serous histological subtype. Frequent CNA aberrations targeted many thousands of genes. However, high-level amplicons and homozygous deletions enabled filtering of this list to the most relevant. The large data set enabled refinement of minimal regions and identification of rare amplicons such as at 1p34 and 20q11. We performed a novel co-occurrence analysis to assess cooperation and exclusivity of CNAs and analysed their relationship to patient outcome. Positive associations were identified between gains on 19 and 20q, gain of 20q and loss of X, and between several regions of loss, particularly 17q. We found weak correlations of CNA at genomic loci such as 19q12 with clinical outcome. We also assessed genomic instability measures and found a correlation of the number of higher amplitude gains with poorer overall survival. By assembling the largest collection of ovarian copy number data to date, we have been able to identify the most frequent aberrations and their interactions.
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