The relationship of TP53 R72P polymorphism to disease outcome and TP53 mutation in myelodysplastic syndromes

Nonsynonymous TP53 exon 4 single-nucleotide polymorphism (SNP), R72P, is linked to cancer and mutagen susceptibility. R72P associations with specific cancer risk, particularly hematological malignancies, have been conflicting. Myelodysplastic syndrome (MDS) with chromosome 5q deletion is characterized by erythroid hypoplasia arising from lineage-specific p53 accumulation resulting from ribosomal insufficiency. We hypothesized that apoptotically diminished R72P C-allele may influence predisposition to del(5q) MDS. Bone marrow and blood DNA was sequenced from 705 MDS cases (333 del(5q), 372 non-del(5q)) and 157 controls. Genotype distribution did not significantly differ between del(5q) cases (12.6% CC, 38.1% CG, 49.2% GG), non-del(5q) cases (9.7% CC, 44.6% CG, 45.7% GG) and controls (7.6% CC, 37.6% CG, 54.8% GG) (P = 0.13). Allele frequency did not differ between non-del(5q) and del(5q) cases (P = 0.91) but trended towards increased C-allele frequency comparing non-del(5q) (P = 0.08) and del(5q) (P = 0.10) cases with controls. Median lenalidomide response duration increased proportionate to C-allele dosage in del(5q) patients (2.2 (CC), 1.3 (CG) and 0.89 years (GG)). Furthermore, C-allele homozygosity in del(5q) was associated with prolonged overall and progressionfree survival and non-terminal interstitial deletions that excluded 5q34, whereas G-allele homozygozity was associated with inferior outcome and terminal deletions involving 5q34 (P = 0.05). These findings comprise the largest MDS R72P SNP analysis

Exploring Persona-Scenarios - Using Storytelling to Create Design Ideas

International audienceThis paper explores the persona-scenario method by investigating how the method can support project participants in generating shared understandings and design ideas. As persona-scenarios are stories we draw on narrative theory to define what a persona-scenario is and which narrative elements it should consist of. Based on an empirical study a key finding is that despite our inherent human ability to construct, tell, and interpret stories it is not easy to write and present a good, coherent, and design-oriented story without methodical support. The paper therefore contributes with guidelines that delineate a) what a design-oriented persona-scenario should consist of (product) and b) how to write it (procedure) in order to generate and validate as many, new, and shared understandings and design ideas as possible (purpose). The purpose of the guidelines is to facilitate the construction of persona-scenarios as good, coherent stories, which make sense to the storytellers and to the audience - and which therefore generate many, new, and shared understandings and design ideas