37 research outputs found
Recurrent intragenic rearrangements of EGFR and BRAF in soft tissue tumors of infants.
Soft tissue tumors of infancy encompass an overlapping spectrum of diseases that pose unique diagnostic and clinical challenges. We studied genomes and transcriptomes of cryptogenic congenital mesoblastic nephroma (CMN), and extended our findings to five anatomically or histologically related soft tissue tumors: infantile fibrosarcoma (IFS), nephroblastomatosis, Wilms tumor, malignant rhabdoid tumor, and clear cell sarcoma of the kidney. A key finding is recurrent mutation of EGFR in CMN by internal tandem duplication of the kinase domain, thus delineating CMN from other childhood renal tumors. Furthermore, we identify BRAF intragenic rearrangements in CMN and IFS. Collectively these findings reveal novel diagnostic markers and therapeutic strategies and highlight a prominent role of isolated intragenic rearrangements as drivers of infant tumors
Drug sensitivity profiling of 3D tumor tissue cultures in the pediatric precision oncology program INFORM
The international precision oncology program INFORM enrolls relapsed/refractory pediatric cancer patients for comprehensive molecular analysis. We report a two-year pilot study implementing ex vivo drug sensitivity profiling (DSP) using a library of 75â78 clinically relevant drugs. We included 132 viable tumor samples from 35 pediatric oncology centers in seven countries. DSP was conducted on multicellular fresh tumor tissue spheroid cultures in 384-well plates with an overall mean processing time of three weeks. In 89 cases (67%), sufficient viable tissue was received; 69 (78%) passed internal quality controls. The DSP results matched the identified molecular targets, including BRAF, ALK, MET, and TP53 status. Drug vulnerabilities were identified in 80% of cases lacking actionable (very) high-evidence molecular events, adding value to the molecular data. Striking parallels between clinical courses and the DSP results were observed in selected patients. Overall, DSP in clinical real-time is feasible in international multicenter precision oncology programs
OTHR-04. Development of a functional plattform for real-time personalized drug sensitivity profiling of patient-derived 3D fresh tumor tissue cultures in the pediatric precision oncology program INFORM [Abstract]
Drug sensitivity profiling of 3D tumor tissue cultures in the pediatric precision oncology program INFORM
The international precision oncology program INFORM enrolls relapsed/refractory pediatric cancer patients for comprehensive molecular analysis. We report a two-year pilot study implementing ex vivo drug sensitivity profiling (DSP) using a library of 75-78 clinically relevant drugs. We included 132 viable tumor samples from 35 pediatric oncology centers in seven countries. DSP was conducted on multicellular fresh tumor tissue spheroid cultures in 384-well plates with an overall mean processing time of three weeks. In 89 cases (67%), sufficient viable tissue was received; 69 (78%) passed internal quality controls. The DSP results matched the identified molecular targets, including BRAF, ALK, MET, and TP53 status. Drug vulnerabilities were identified in 80% of cases lacking actionable (very) high-evidence molecular events, adding value to the molecular data. Striking parallels between clinical courses and the DSP results were observed in selected patients. Overall, DSP in clinical real-time is feasible in international multicenter precision oncology programs.Peer reviewe
Clinical impact of postâinduction resolution of pulmonary lesions in metastatic Ewing sarcoma
Differentialdiagnose Augenschwellung - Rhabdomyosarkom der Orbita - Prognoseverschlechterung durch initial falsches Àrztliches Handeln
MRT- und Sonographie-gesteuerte tru-cut Biopsien zur Erstdiagnose extrakranieller Weichteiltumore im Kindesalter
Clinical characteristics and outcomes for children, adolescents and young adults with âCIC-fusedâ or âBCOR-rearrangedâ soft tissue sarcomas: A multi-institutional European retrospective analysis
Background: In certain rare undifferentiated small round cell sarcomas new specific molecular CIC-DUX4/other partner, BCOR-CCNB3/other partner, YWHAE fusions, or BCOR-ITD (internal tandem duplication) were identified. These new âCIC fusedâ (CIC-fused/ATXN1::NUTM1) and âBCOR rearrangedâ (BCOR fused/ITD/ YWHAE) soft tissue sarcomas (STS) are not well described. Methods: Multi-institutional European retrospective analysis of young patients (0â24 years) with CIC-fused and BCOR rearranged STS. Results: Overall, out of the 60 patients selected, the fusion status was CIC-fused (n = 29), ATXN1::NUTM1 (n = 2), BCOR::CCNB3 (n = 18), BCOR-ITD (n = 7), and YWHAE (n = 3), MAML::BCOR STS (n = 1). The main primaries were abdomen-pelvic (n = 23) and limbs (n = 18). Median age was 14 years (0.9â23.8) and 0.9 (0.1â19.1) for CIC-fused and BCOR-rearranged groups, respectively (n = 29; p 5 cm) but only six had lymph node involvement. Patients received mainly chemotherapy (n = 57), local surgery (n = 50), and/or radiotherapy (n = 34). After a median follow-up of 47.1 months (range, 3.4â230), 33 (52%) patients had an event and 23 patients died. Three-year event-free survivals were 44.0% (95% CI 28.7â67.5) and 41.2% (95% CI 25.4â67.0) for CIC and BCOR groups (p = 0.97), respectively. Three-year overall survivals were 46.3% (95% CI 29.6â72.4) and 67.1% (95% CI 50.4â89.3; p = 0.24), respectively. Conclusions: Pediatric patients often present with large tumors and metastatic disease, especially CIC sarcomas. Overall outcome is dismal. New treatment options are needed