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951 results on '"Behrens H"'

32. Multiscale heterogeneity in gastric adenocarcinoma evolution is an obstacleto precision medicine

Author

Röcken, C., Amallraja, A., Halske, C., Opašić, L., Traulsen, A., Behrens, H., Krüger, S., Liu, A., Haag, J., Egberts, J., Rosenstiel, P., and Meissner, T.

Abstract

Purpose: Cancer is a somatic evolutionary disease. Using multiregional whole exome sequencing, we tested the effect of somatic evolution on intratumoral heterogeneity and its putative clinical and biological implications in adenocarcinomas of the stomach and gastroesophageal junction (GC). Patients and Methods: The study comprised a prospective discovery cohort of 9 and a validation cohort of 463 GCs. Multiregional whole-exome sequencing was done using 48 tumor samples (range: 3-10 tumor samples/patient) of the discovery cohort. Results: In total, the discovery cohort harbored 16,537 non-synonymous mutations (mutations/sample: median n=159; mutations/patient: median n=369). Intratumoral heterogeneity of somatic mutations and copy number variants were present in all tumors of the discovery cohort. 53-91% of the non-synonymous mutations were not present in each patient’s sample; 399 genes harbored 2-4 different non-synonymous mutations in the same patient; 175 genes showed copy number variations, the majority being heterogeneous, including CD274 (PD-L1). Multi-sample tree-based analyses provided evidence for branched evolution being most complex in a microsatellite instable GC. The analysis of the mode of evolution showed a high degree of heterogeneity in deviation from neutrality within each tumor. Studies on the validation cohort showed that the subclonal loss of SMAD4 is an independent predictor for poor patient outcome in Caucasian patients. Conclusions: Neutral and non-neutral somatic evolution shape the mutational landscape in GC. It leads to complex spatial intratumoral heterogeneity and may have profound effects on patient management. It provides crucial information for an individualized understanding of clinical prognosis and therapeutic options in GC patients.

Published
2020

49. Compositional dependence of H2O solubility along the joins NaAlSi3O8-KAlSi3O8, NaAlSi3O8-LiAlSi3O8, and KAlSi3O8-LiAlSi3O8

Author

Romano, C., Dingwell, D.B., Behrens, H., and Dolfi, D.

Subjects
Silicates -- Research, Solubility -- Research, Crystals -- Structure, Phase rule and equilibrium -- Research, Earth sciences
Abstract

The composition-dependence of the solubility of [H.sub.2]O in silicate melts along the binary joins NaAl[Si.sub.3][O.sub.8]-KAl[Si.sub.3][O.sub.8], NaAl[Si.sub.3][O.sub.8]-LiAl[Si.sub.3][O.sub.8], and KAl[Si.sub.3][O.sub.8]-LiAl[Si.sub.3][O.sub.8] has been determined at 2 kbar and 1040 [degrees] C. The study involved 1 atm dry oxide fusion, hydrothermal saturation, isobaric rapid quench and macroscopic analysis for [H.sub.2]O using Karl Fischer titration (KFT) and microscopic investigation of homogeneity using infrared absorption spectroscopy, respectively. The solubility of [H.sub.2]O in these melts increases in the order KAl[Si.sub.3][O.sub.8] (5.12 wt%) < NaAl[Si.sub.3][O.sub.8] (6.03 wt%) < LiAl[Si.sub.3][O.sub.8] (7.32 wt%). The total relative weight percent variation in solubility is 43%, which corresponds to a relative mole percent variation of 23%. Along the joins, small but systematic deviations from additivity are observed at the 1[Sigma] uncertainty level. These deviations are positive on the NaAl[Si.sub.3][O.sub.8]-KAl[Si.sub.3][O.sub.8] join but negative on the LiAl[Si.sub.3][O.sub.8]-bearing joins. The present results confirm the early suggestion of Voigt et al. (1981) that solubility variation along the NaAl[Si.sub.3][O.sub.8]-KAl[Si.sub.3][O.sub.8] join is nonlinear and disagree in detail with the equimolal approximation of Burnham (1975, 1981) and Burnham and Davis (1974). Models of [H.sub.2]O solubility must take into account not only the nonequimolal solubility of [H.sub.2]O in feldspathic melts but also nonlinear binary variations as well. We interpret the relative solubilities of the end-member compositions in terms of the relative stability of the tectosilicate melt structure and the nonlinearities along the joins in terms of the next-nearest neighbor distributions of Al and Si in these melts.

Published
1996

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