Association between Acquired Uniparental Disomy and Homozygous Mutations and HER2/ER/PR Status in Breast Cancer

Background: Genetic alterations in cellular signaling networks are a hallmark of cancer, however, effective methods to discover them are lacking. A novel form of abnormality called acquired uniparental disomy (aUPD) was recently found to pinpoint the region of mutated genes in various cancers, thereby identifying the region for next-generation sequencing. Methods/Principal Findings: We retrieved large genomic data sets from the Gene Expression Omnibus database to perform genome-wide analysis of aUPD in breast tumor samples and cell lines using approaches that can reliably detect aUPD. Aupd was identified in 52.29% of the tumor samples. The most frequent aUPD regions were located at chromosomes 2q, 3p, 5q, 9p, 9q, 10q, 11q, 13q, 14q and 17q. We evaluated the data for any correlation between the most frequent aUPD regions and HER2/neu, ER, and PR status, and found a statistically significant correlation between the recurrent regions of aUPD and triple negative (TN) breast cancers. aUPD at chromosome 17q (VEZF1, WNT3), 3p (SUMF1, GRM7), 9p (MTAP, NFIB) and 11q (CASP1, CASP4, CASP5) are predictors for TN. The frequency of aUPD was found to be significantly higher in TN breast cancer cases compared to HER2/neu-positive and/or ER or PR-positive cases. Furthermore, using previously published mutation data, we found TP53 homozygously mutated in cell lines having aUPD in that locus. Conclusions/Significance: We conclude that aUPD is a common and non-random molecular feature of breast cancer that is most prominent in triple negative cases. As aUPD regions are different among the main pathological subtypes, specific aUPD regions may aid the sub-classification of breast cancer. In addition, we provide statistical support using TP53 as an example that identifying aUPD regions can be an effective approach in finding aberrant genes. We thus conclu

Weight-Loss Maintenance in Overweight Individuals One to Five Years Following Successful Completion of a Commercial Weight Loss Program

OBJECTIVE: To determine weight loss maintenance among participants in a commercial weight loss program (Weight Watchers) who had reached their goal weights 1-5 y previously. DESIGN: A national sample (n=1002) was surveyed by phone to obtain demographic and weight-related information. An oversample (n=258) was recruited and weighed in person to develop a correction factor for self-reported weights in the national sample. RESULTS: Based on corrected weights, weight regain from 1 to 5 y following weight loss ranged between 31.5 and 76.5%. At 5 y, 19.4% were within 5 lb of goal weight, 42.6% maintained a loss of 5% or more, 18.8% maintained a loss of 10% or more, and 70.3% were below initial weight. CONCLUSIONS: These results are not directly comparable to those obtained in clinical settings because of differences in the populations studied. Nonetheless, they suggest that the long-term prognosis for weight maintenance among individuals who reach goal weight in at least one commercial program is better than that suggested by existing research

The Endocrinology of the Stress Response in Fish

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