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- Duran-Ferrer, Marti, et al.
(författare)
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The proliferative history shapes the DNA methylome of B-cell tumors and predicts clinical outcome
- 2020
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Ingår i: NATURE CANCER. - : Springer Nature. - 2662-1347. ; 1:11, s. 1066-1081
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Tidskriftsartikel (refereegranskat)abstract
- We report a systematic analysis of the DNA methylation variability in 1,595 samples of normal cell subpopulations and 14 tumor subtypes spanning the entire human B-cell lineage. Differential methylation among tumor entities relates to differences in cellular origin and to de novo epigenetic alterations, which allowed us to build an accurate machine learning-based diagnostic algorithm. We identify extensive individual-specific methylation variability in silenced chromatin associated with the proliferative history of normal and neoplastic B cells. Mitotic activity generally leaves both hyper- and hypomethylation imprints, but some B-cell neoplasms preferentially gain or lose DNA methylation. We construct a DNA-methylation-based mitotic clock, called epiCMIT, whose lapse magnitude represents a strong independent prognostic variable in B-cell tumors and is associated with particular driver genetic alterations. Our findings reveal DNA methylation as a holistic tracer of B-cell tumor developmental history, with implications in differential diagnosis and the prediction of clinical outcome. Martin-Subero and colleagues analyze DNA methylation patterns in B-cell tumors and their normal cells of origin, and develop epiCMIT, a methylation-based mitotic clock with prognostic relevance.
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- Queiros, Sandro, et al.
(författare)
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Multi-centre validation of an automatic algorithm for fast 4D myocardial segmentation in cine CMR datasets
- 2016
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Ingår i: European Heart Journal Cardiovascular Imaging. - : OXFORD UNIV PRESS. - 2047-2404 .- 2047-2412. ; 17:10, s. 1118-1127
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Tidskriftsartikel (refereegranskat)abstract
- Aims Quantitative analysis of cine cardiac magnetic resonance (CMR) images for the assessment of global left ventricular morphology and function remains a routine task in clinical cardiology practice. To date, this process requires user interaction and therefore prolongs the examination (i.e. cost) and introduces observer variability. In this study, we sought to validate the feasibility, accuracy, and time efficiency of a novel framework for automatic quantification of left ventricular global function in a clinical setting. Methods and results Analyses of 318 CMR studies, acquired at the enrolment of patients in a multi-centre imaging trial (DOPPLER-CIP), were performed automatically, as well as manually. For comparative purposes, intra-and inter-observer variability was also assessed in a subset of patients. The extracted morphological and functional parameters were compared between both analyses, and time efficiency was evaluated. The automatic analysis was feasible in 95% of the cases (302/318) and showed a good agreement with manually derived reference measurements, with small biases and narrow limits of agreement particularly for end-diastolic volume (-4.08 +/- 8.98 mL), end-systolic volume (1.18 +/- 9.74 mL), and ejection fraction (-1.53 +/- 4.93%). These results were comparable with the agreement between two independent observers. A complete automatic analysis took 5.61 +/- 1.22 s, which is nearly 150 times faster than manual contouring (14 +/- 2 min, P amp;lt; 0.05). Conclusion The proposed automatic framework provides a fast, robust, and accurate quantification of relevant left ventricular clinical indices in real-world cine CMR images.
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- Tsagiopoulou, Maria, et al.
(författare)
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DNA methylation profiles in chronic lymphocytic leukemia patients treated with chemoimmunotherapy
- 2019
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Ingår i: Clinical Epigenetics. - : BMC. - 1868-7083 .- 1868-7075. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Background: In order to gain insight into the contribution of DNA methylation to disease progression of chronic lymphocytic leukemia (CLL), using 450K Illumina arrays, we determined the DNA methylation profiles in paired pre-treatment/relapse samples from 34 CLL patients treated with chemoimmunotherapy, mostly (n = 31) with the fludarabine-cyclophosphamide-rituximab (FCR) regimen.Results: The extent of identified changes in CLL cells versus memory B cells from healthy donors was termed "epigenetic burden" (EB) whereas the number of changes between the pre-treatment versus the relapse sample was termed "relapse changes" (RC). Significant (p < 0.05) associations were identified between (i) high EB and short time-to-first-treatment (TTFT); and, (ii) few RCs and short time-to-relapse. Both the EB and the RC clustered in specific genomic regions and chromatin states, including regulatory regions containing binding sites of transcription factors implicated in B cell and CLL biology.Conclusions: Overall, we show that DNA methylation in CLL follows different dynamics in response to chemoimmunotherapy. These epigenetic alterations were linked with specific clinical and biological features.
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