Familienwissenschaftliche Rhetorik eine explorative Analyse ausgewaehlter Texte

Available from Badische LB Karlsruhe(31) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman

Familienwissenschaftliche Rhetorik Eine explorative Analyse ausgewaehlter Texte

Die vorliegende Arbeit wird als ein Versuch betrachtet, im Bereich der familienwissenschaftlichen Forschung und in Fortsetzung von Ueberlegungen zur allgemeinen Familienrhetorik, verschiedene Facetten der wissenschaftlichen Rhetorik und ihrer Unvermeidbarkeit darzustellen. Jeder der untersuchten Texte stellt den Versuch dar, die gegenwaertige Situation von Familie in Deutschland zu definieren, wobei die Ergebnisse offensichtlich unterschiedlich sind. (SH2)SIGLEAvailable from Badische LB Karlsruhe(31) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman

Genomic EWS-FLI1 Fusion Sequences in Ewing Sarcoma Resemble Breakpoint Characteristics of Immature Lymphoid Malignancies

Chromosomal translocations between the EWS gene and members of the ETS gene family are characteristic molecular features of the Ewing sarcoma. The most common translocation t(11;22)(q24;q12) fuses the EWS gene to FLI1, and is present in 85–90% of Ewing sarcomas. In the present study, a specifically designed multiplex long-range PCR assay was applied to amplify genomic EWS-FLI1 fusion sites from as little as 100 ng template DNA. Characterization of the EWS-FLI1 fusion sites of 42 pediatric and young adult Ewing sarcoma patients and seven cell lines revealed a clustering in the 5′ region of the EWS-breakpoint cluster region (BCR), in contrast to random distribution of breakpoints in the FLI1-BCR. No association of breakpoints with various recombination-inducing sequence motifs was identified. The occurrence of small deletions and duplications at the genomic junction is characteristic of involvement of the non-homologous end-joining (NHEJ) repair system, similar to findings at chromosomal breakpoints in pediatric leukemia and lymphoma

Genetic alterations in human papillomavirus-associated oropharyngeal squamous cell carcinoma of patients with treatment failure

Objectives: Despite improved survival rates of patients with HPV-associated OPSCC, a subset has distant metastasis or develops local recurrence during follow-up. To investigate potential underlying genetic alterations, we analyzed patients with HPV-driven OPSCC who suffered from recurrence in comparison to matching pairs with successful tumor control. Materials and methods: We performed chromosomal copy number analyses and targeted next generation sequencing using a custom panel comprising genes that are frequently mutated in HPV-associated OPSCC. Results: Specific differences regarding chromosomal aberrations were not observed between both groups. In HPV-driven OPSCC from patients with recurrence we found higher mutation rates compared to patients with successful tumor control. Especially mutation rates of HRAS (p <= 0.05) PIK3R1, STK11 and TP63 (p <= 0.1 each) were statistically significant or trending towards significance. The respective genes can be linked to transcription factors and signaling pathways involved in cell cycle regulation, proliferation and survival. Additionally, combinations of alterations were observed on chromosomes 16 and 19, which might also influence outcome. Conclusion: Patients with HPV-driven OPSCC who develop recurrence or have metastasis may be defined by genetic alterations that might be responsible for poor outcome after standard therapy. This might be of importance for stratification in future de-escalation and targeted therapy

Mutation patterns in recurrent and/or metastatic oropharyngeal squamous cell carcinomas in relation to human papillomavirus status

Patients with HPV-driven (HPV+) oropharyngeal squamous cell carcinoma (OPSCC) have a significantly improved overall survival compared to patients with HPV-negative (HPV-) OPSCC. Nevertheless, 13%-25% of patients with HPV+OPSCC develop local/distant recurrence (LDR) and have a course of disease similar to HPV-OPSCC. We hypothesize that HPV+OPSCCs of patients with LDR have a mutation frequency and pattern similar to HPV-OPSCCs, which is associated with severe outcome. We performed targeted next-generation sequencing using a customized gene panel and compared data from 56 matched HPV+and HPV-OPSCC of patients with/without LDR regarding protein-altering variants. Despite improved overall survival of patients with HPV+OPSCC, those who develop LDR show a strongly reduced survival rate that is similar or even worse compared to HPV-OPSCC patients. Overall, the number of mutations was similar in OPSCC of patients with and without LDR. In total and with respect to TP53, HPV-OPSCC had significantly more protein-altering mutations than HPV+OPSCC. The number of mutations was similar in HPV-OPSCC of patients with and without LDR with the exception of FAT1, which was mutated more frequently in patients without LDR. In HPV+OPSCC, HRAS, PIK3R1, STK11 and TP63 were more frequently mutated in patients with LDR compared to patients without. HPV+OPSCC of patients with LDR have a similar mutation pattern as HPV-OPSCC, except TP53, which was mutated to a significantly lower extent. In conclusion, HPV-and HPV+OPSCC with LDR have similar mutation counts in the analyzed genes. We suspect that the number of mutations is not causal for disease progression, rather specific mutations could be important

Plasma Cell-Free Human Papillomavirus Oncogene E6 and E7 DNA Predicts Outcome in Oropharyngeal Squamous Cell Carcinoma

Persistent human papillomavirus (HPV) infection is associated with the development of oropharyngeal squamous cell carcinoma (OPSCC), and increasing incidences of OPSCC are reported. The generally favorable treatment outcome in patients with HPV-driven OPSCC has brought de-escalation of treatment into discussion. Nevertheless, 13% to 25% develop a relapse within two years after current standard treatment. New biomarkers are urgently required to monitor therapy response, tumor burden, and minimal residual disease during follow-up. This observational study examined 50 patients with OPSCC to investigate plasma cell-free (cf) HPV-DNA derived from tumor cells before therapy and during follow-up. Real-time quantitative PCR was applied to quantify the DNA concentration of HPV oncogenes E6 and E7. A total of 85.7% of pretreatment samples from patients with HPV-driven OPSCC (n = 28) were positive for at least one marker, and cfHPV-DNA concentration increased with tumor size. Virtually no signals were detected in HPV-negative OPSCC patients (n = 20;

Breakpoint distribution in the BCR of <i>EWS</i> and <i>FLl1</i>.

<p>(A) Vertical bars above or below the breakpoint regions indicate individual breakpoint positions of Ewing sarcoma patients. Black boxes represent exons, and gray boxes correspond to repeat elements. (B) Results of Kernel density analysis (dashed line = breakpoint density; gray line = lower limit of 95% confidence band determined by bootstrapping procedure; black line = 95% confidence interval of a density function resulting from simulations at randomly distributed pseudo-breakpoints). X-axes indicate the BCR nucleotide positions within the respective reference gene. (C) Scatterblot of gender-specific <i>EWS-FLI1</i> breakpoints. Circles represent female, and squares represent male subjects. (D) Number of microhomologies and filler nucleotides at <i>EWS-FLI1</i> (der22; black bar) and <i>FLI1-EWS</i> (der11; gray bar) fusion sites. Each bar on the x-axis represents one individual.</p

Genomic <em>EWS</em>-<em>FLI1</em> Fusion Sequences in Ewing Sarcoma Resemble Breakpoint Characteristics of Immature Lymphoid Malignancies

<div><p>Chromosomal translocations between the <i>EWS</i> gene and members of the <i>ETS</i> gene family are characteristic molecular features of the Ewing sarcoma. The most common translocation t(11;22)(q24;q12) fuses the <i>EWS</i> gene to <i>FLI1</i>, and is present in 85–90% of Ewing sarcomas. In the present study, a specifically designed multiplex long-range PCR assay was applied to amplify genomic <i>EWS-FLI1</i> fusion sites from as little as 100 ng template DNA. Characterization of the <i>EWS-FLI1</i> fusion sites of 42 pediatric and young adult Ewing sarcoma patients and seven cell lines revealed a clustering in the 5′ region of the <i>EWS</i>-breakpoint cluster region (BCR), in contrast to random distribution of breakpoints in the <i>FLI1</i>-BCR. No association of breakpoints with various recombination-inducing sequence motifs was identified. The occurrence of small deletions and duplications at the genomic junction is characteristic of involvement of the non-homologous end-joining (NHEJ) repair system, similar to findings at chromosomal breakpoints in pediatric leukemia and lymphoma.</p> </div

Plasma Cell-Free Human Papillomavirus Oncogene<i> E6</i> and<i> E7</i> DNA Predicts Outcome in Oropharyngeal Squamous Cell Carcinoma

Persistent human papillomavirus (HPV) infection is associated with the development of oropharyngeal squamous cell carcinoma (OPSCC), and increasing incidences of OPSCC are reported. The generally favorable treatment outcome in patients with HPV-driven OPSCC has brought de-escalation of treatment into discussion. Nevertheless, 13% to 25% develop a relapse within two years after current standard treatment. New biomarkers are urgently required to monitor therapy response, tumor burden, and minimal residual disease during follow-up. This observational study examined 50 patients with OPSCC to investigate plasma cell-free (cf) HPV-DNA derived from tumor cells before therapy and during follow-up. Real-time quantitative PCR was applied to quantify the DNA concentration of HPV oncogenes E6 and E7. A total of 85.7% of pretreatment samples from patients with HPV-driven OPSCC (n = 28) were positive for at least one marker, and cfHPV-DNA concentration increased with tumor size. Virtually no signals were detected in HPV-negative OPSCC patients (n = 20; P <= 0.001). Patients without clinical evidence of recurrence had significantly reduced cfHPV-DNA concentrations after therapy (P <= 0.001). Conversely, cfHPV-DNA levels increased or remained above threshold in five patients who had residual disease or developed recurrence. In conclusion, plasma cfHPV-DNA detection correlates with the clinical course of disease in patients with HPV-driven OPSCC. Consequently, extensive clinical investigation should be considered if cfHPV-DNA is detected during follow-up of patients with HPV-driven OPSCC