Female Chromosome X Mosaicism is Age-Related and Preferentially Affects the Inactivated X Chromosome

To investigate large structural clonal mosaicism of chromosome X, we analysed the SNP microarray intensity data of 38,303 women from cancer genome-wide association studies (20,878 cases and 17,425 controls) and detected 124 mosaic X events 4 2 Mb in 97 (0.25%) women. Here we show rates for X-chromosome mosaicism are four times higher than mean autosomal rates; X mosaic events more often include the entire chromosome and participants with X events more likely harbour autosomal mosaic events. X mosaicism frequency increases with age (0.11% in 50-year olds; 0.45% in 75-year olds), as reported for Y and autosomes. Methylation array analyses of 33 women with X mosaicism indicate events preferentially involve the inactive X chromosome. Our results provide further evidence that the sex chromosomes undergo mosaic events more frequently than autosomes, which could have implications for understanding the underlying mechanisms of mosaic events and their possible contribution to risk for chronic diseases

Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome

To investigate large structural clonal mosaicism of chromosome X, we analysed the SNP microarray intensity data of 38,303 women from cancer genome-wide association studies (20,878 cases and 17,425 controls) and detected 124 mosaic X events >2 Mb in 97 (0.25%) women. Here we show rates for X-chromosome mosaicism are four times higher than mean autosomal rates; X mosaic events more often include the entire chromosome and participants with X events more likely harbour autosomal mosaic events. X mosaicism frequency increases with age (0.11% in 50-year olds; 0.45% in 75-year olds), as reported for Y and autosomes. Methylation array analyses of 33 women with X mosaicism indicate events preferentially involve the inactive X chromosome. Our results provide further evidence that the sex chromosomes undergo mosaic events more frequently than autosomes, which could have implications for understanding the underlying mechanisms of mosaic events and their possible contribution to risk for chronic diseases

Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome

To investigate large structural clonal mosaicism of chromosome X, we analysed the SNP microarray intensity data of 38,303 women from cancer genome-wide association studies (20,878 cases and 17,425 controls) and detected 124 mosaic X events42Mb in 97 (0.25%) women. Here we show rates for X-chromosome mosaicism are four times higher than mean autosomal rates; X mosaic events more often include the entire chromosome and participants with X events more likely harbour autosomal mosaic events. X mosaicism frequency increases with age (0.11% in 50-year olds; 0.45% in 75-year olds), as reported for Y and autosomes. Methylation array analyses of 33 women with X mosaicism indicate events preferentially involve the inactive X chromosome. Our results provide further evidence that the sex chromosomes undergo mosaic events more frequently than autosomes, which could have implications for understanding the underlying mechanisms of mosaic events and their possible contribution to risk for chronic diseases

Alternate migration strategies of eastern monarch butterflies revealed by stable isotopes

Alternative life history strategies are mechanisms by which organisms are able to maximize fitness across a range of environmental conditions. Fitness is maximized by different strategies depending on context, resulting in trade-offs between life history strategies. Monarch butterflies (Danaus plexippus) employ both migratory and resident life history strategies. Since residents breed throughout the year, but migrants overwinter in reproductive diapause, there are fitness trade-offs between the two strategies. We used stable isotope analysis to evaluate the geographic origins of monarchs in a yearround population in south Florida. Based on stable isotope profiles of hydrogen and carbon (δ2H and δ13C values), we found that 48% (16/33) of monarchs collected in south Florida are migrants that originated from outside the sampling region. Migrants had a larger wing length than residents; thus, switching to a resident strategy could alter their probability of reproductive success. Further work is needed to investigate the mechanism underlying this pattern, but these findings show that alternate life history strategies and sex-specific behaviors are underexplored factors influencing monarch migration and evolution

Validation of a biological score to predict response in chronic lymphocytic leukemia patients treated front-line with bendamustine and rituximab

During the the last two decades several biological prognostic markers have been identified in chronic lymphocytic leukemia (CLL) [1]. Some, like the IGHV mutational status and TP53 disruption, are also predictive of response to chemo-immunotherapy [2,3,4,5,6]. Rossi et al. reported an observational retrospective analysis on 404 CLL patients treated front-line with fludarabine-cyclophosphamide-rituximab (FCR) [6]. Based on the IGHV mutational status and FISH cytogenetics, patients were stratified into low risk (mutated IGHV and no adverse FISH cytogenetics [del(17p), del(11q)]), intermediate risk (unmutated IGHV and/or del11q in the absence of del17p), and high risk (del17p independent of co-occurring del11q or unmutated IGHV). This simple biologically based prognostic score based on the combination of three widely utilized biomarkers allowed to stratify patients with a significantly different progression-free survival (PFS) and overall survival (OS) after FCR treatment. In addition, they also demonstrated that low-risk patients had a durable remissions after FCR, with a life expectancy overlapping that observed in the age-matched general population [6]. Similarly, Laurenti et al. recently published a retrospective study on 102 patients with CLL treated front-line with chlorambucil-rituximab [7]. This analysis also showed that the above-mentioned biological score could distinguish patients with a different PFS. A trend toward a better OS was also observed

Predictive value of the CLL-IPI in CLL patients receiving chemo-immunotherapy as first-line treatment

An international collaboration has led to the development of a comprehensive tool [CLL\u2010IPI international prognostic index for CLL] for the predicting of overall survival (OS) in chronic lymphocytic leukemia (CLL).1 CLL\u2010IPI was based on data collected from 3500 CLL patients and was based on the following parameters: TP53 deletion and/or mutation, IGHV mutational status, \u3b22\u2010microglobulin plasma levels, clinical stage, and age. CLL\u2010IPI provides the means to stratify CLL patients in the daily clinical practice (Table S1).1 Although validated for OS2-4 and time to first treatment (TTFT),5 the predictive value of CLL\u2010IPI on progression\u2010free survival (PFS) has until now only been demonstrated in a single study on patients treated with chlorambucil (CLB), as monotherapy, or in combination with obinutuzumab or rituximab, as a first\u2010line approach (CLL11 study),6 and presented as a poster at the annual meeting of the American Society of Hematology (ASH) in 2016

Predictive value of the CLL-IPI in CLL patients receiving chemo-immunotherapy as first-line treatment

An international collaboration has led to the development of a comprehensive tool [CLL-IPI international prognostic index for CLL] for the predicting of overall survival (OS) in chronic lymphocytic leukemia (CLL).1 CLL-IPI was based on data collected from 3500 CLL patients and was based on the following parameters: TP53 deletion and/or mutation, IGHV mutational status, \u3b22-microglobulin plasma levels, clinical stage, and age. CLL-IPI provides the means to stratify CLL patients in the daily clinical practice (Supplementary Table 1).1 Although validated for OS2-4 and time to first treatment (TTFT),5 the predictive value of CLL-IPI on progression-free survival (PFS) has until now only been demonstrated in a single study on patients treated with chlorambucil (CLB), as monotherapy, or in combination with obinutuzumab or rituximab, as a first-line approach (CLL11 study),6 and presented as a poster at the annual meeting of the American Society of Hematology (ASH) in 2016. This article is protected by copyright. All rights reserved