Complex chromosomal rearrangements by single catastrophic pathogenesis in NUT midline carcinoma.

Background: Nuclear protein in testis (NUT) midline carcinoma (NMC) is a rare aggressive malignancy often occurring in the tissues of midline anatomical structures. Except for the pathognomonic BRD3/4-NUT rearrangement, the comprehensive landscape of genomic alterations in NMCs has been unexplored. Patients and methods: We investigated three NMC cases, including two newly diagnosed NMC patients in Seoul National University Hospital, and a previously reported cell line (Ty-82). Whole-genome and transcriptome sequencing were carried out for these cases, and findings were validated by multiplex fluorescence in situ hybridization and using individual fluorescence probes. Results: Here, we present the first integrative analysis of whole-genome sequencing, transcriptome sequencing and cytogenetic characterization of NUT midline carcinomas. By whole-genome sequencing, we identified a remarkably similar pattern of highly complex genomic rearrangements (previously denominated as chromoplexy) involving the BRD3/4-NUT oncogenic rearrangements in two newly diagnosed NMC cases. Transcriptome sequencing revealed that these complex rearrangements were transcribed as very simple BRD3/4-NUT fusion transcripts. In Ty-82 cells, we also identified a complex genomic rearrangement involving the BRD4-NUT rearrangement underlying the simple t(15;19) karyotype. Careful inspections of rearrangement breakpoints indicated that these rearrangements were likely attributable to single catastrophic events. Although the NMC genomes had >3000 somatic point mutations, canonical oncogenes or tumor suppressor genes were rarely affected, indicating that they were largely passenger events. Mutational signature analysis showed predominant molecular clock-like signatures in all three cases (accounting for 54%-75% of all base substitutions), suggesting that NMCs may arise from actively proliferating normal cells. Conclusion: Taken together, our findings suggest that a single catastrophic event in proliferating normal cells could be sufficient for neoplastic transformation into NMCs.

[Application of the Portuguese version of the abbreviated instrument of quality life WHOQOL-bref]. / Aplicação da versão em português do instrumento abreviado de avaliação da qualidade de vida "WHOQOL-bref"

INTRODUCTION: The need of short instruments to evaluate Quality of life determines World Health Organization Quality of Life Group (WHOQOL Group) to develop an abbreviated version of the WHOQOL-100, the WHOQOL-bref. The objective is to present the Brazilian field trial of the WHOQOL-bref. METHODS: WHOQOL-bref is composed by 26 questions divided in four domains: physical, psychological, social relationships and environment. The evaliation instrument, BDI (beck depression inventory) and BHS (beck hopelessness scale) were used in a 300 subjects sample in Porto Alegre, South Brazil. RESULTS/CONCLUSIONS: The instrument showed a good performance concerning internal consistency, discriminant validity, criterion validity, concurrent validity and test-retest reliability. The intrument allies good psychometric performance and practicity for use which puts it as an interesting option to evaluate quality of life in Brazil.

[Application of the Portuguese version of the instrument for the assessment of quality of life of the World Health Organization (WHOQOL-100)]. / Aplicação da versão em português do instrumento de avaliação de qualidade de vida da organização mundial da saúde (WHOQOL-100).

OBJECTIVE: The WHOQOL group have developed an instrument to evaluate Quality of Life, the WHOQOL-100, available in 20 different languages (WHOQOL Group, 1998). The field trial of the portuguese version of the instrument is presented. METHODS: Two hundred and fifty patients from four main medical areas (Psychiatry, Clinical, Surgery and Ginecology) of the Hospital de Clínicas de Porto Alegre and 50 controls were evaluated with the Portuguese version of the WHO Quality of Life Instrument (WHOQOL-100), Beck Depression Inventory (BDI) and Beck Hopelessness Scale (BHS) in Porto Alegre, south Brazil. RESULTS AND CONCLUSION: The instrument showed a good psychometric performance with good internal consistency, discriminant validity, criterion validity, concurrent validity and reliability. The authors conclude that the intrument is ready for use in Brazil, it being important to evaluate its performance in other regions and with different samples.