Very Long-term Survivorship in Pediatric DIPG: Case Report and Review of the Literature.

Diffuse intrinsic pontine gliomas are lethal tumors with a prognosis generally less than 1 year. Few cases of survivors of 5 years or more have been reported. This case report highlights the journey of a 9.5-year survivor who underwent 3 rounds of focal radiotherapy; she experienced 6 years of progression-free survival following the first round but ultimately succumbed to her disease. An autopsy revealed a favorable IDH1 mutation and the absence of H3K27M. This case reiterates the importance of extensive molecular analyses in diffuse intrinsic pontine gliomas and explores the potential benefit of re-irradiation in patients with positive responses and long periods of remission.

Recurrent primary intracranial sarcoma, DICER1-mutant in a pediatric patient with DICER1 syndrome: the importance of molecular testing.

Pediatric intracranial sarcomas are rare, aggressive tumors with a poor prognosis in general. Here we report the case of a child who was initially diagnosed with a primary intracranial sarcoma, DICER1-mutant; subsequent genetic analyses confirmed a pathogenic germline DICER1 mutation. She received multimodal standard treatments consisting of surgery, radiotherapy and chemotherapy. The tumor recurred 2.5 years later within the surgical cavity. Following the gross tumor resection of this new lesion, the same multimodal standard approach was used. From a molecular perspective, evidence of hyperactivation of the MAPK-kinase pathway with a pathogenic KRAS mutation at both diagnosis and recurrence was present. The patient is currently in remission, 18 months post-end of treatment.

Bevacizumab in the Treatment of Refractory Brain Edema in High-grade Glioma.

We report the case of a 14-year-old boy with a steroid-dependent refractory tumor whose longstanding dexamethasone treatment was successfully discontinued after a course of bevacizumab. The use of bevacizumab despite the absence of clear evidence of radionecrosis allowed a significant decrease in the amount of the brain edema.

Translating the Symptom Screening in Pediatrics Tool (SSPedi) into French and among French-speaking children receiving cancer treatments, evaluating understandability and cultural relevance in a multiple-phase descriptive study.

OBJECTIVES: Symptom Screening in Pediatrics Tool (SSPedi) is a validated approach to measuring bothersome symptoms for English-speaking and Spanish-speaking children with cancer and paediatric haematopoietic stem cell transplantation (HSCT) recipients. Objectives were to translate SSPedi into French, and among French-speaking children receiving cancer treatments, to evaluate understandability and cultural relevance. METHODS: We conducted a multiphase, descriptive study to translate SSPedi into French. Forward translation was performed by four medical translators. After confirming that back translation was satisfactory, we enrolled French-speaking children with cancer and paediatric HSCT recipients at four centres in France and Canada. PRIMARY AND SECONDARY OUTCOME MEASURES: Understandability was evaluated by children themselves who self-reported degree of difficulty, and by two adjudicators who rated incorrectness. Assessment of cultural relevance was qualitative. Participants were enrolled in cohorts of 10. RESULTS: There were 30 children enrolled. Participants were enrolled from Marseille (n=10, 33%), Ottawa (n=1, 3%), Quebec City (n=11, 37%) and Toronto (n=8, 27%). No child reported that it was hard or very hard to complete French SSPedi in the last cohort of 10 participants. Changes to the instrument itself were not required. After enrolment of 30 respondents, the French translation of SSPedi was considered finalised based on self-reported difficulty with understanding, adjudicated incorrect understanding and cultural relevance. CONCLUSIONS: We translated and finalised SSPedi for use by French-speaking children and adolescents receiving cancer treatments. Future work should begin to use the translated version to conduct research and to facilitate clinical care.

MUC16 mucin (CA125) regulates the formation of multicellular aggregates by altering ß-catenin signaling.

After shedding from the primary tumor site, ovarian cancer cells form three-dimensional multicellular aggregates that serve as vehicle for cancer cell dissemination in the peritoneal cavity. MUC16 mucin (CA125) is aberrantly expressed by most advanced serous ovarian cancers and can promote proliferation, migration and metastasis. MUC16 associates with E-cadherin and ß-catenin, two proteins involved in regulation of cell adhesion and the formation of multicellular aggregates. However, the role of MUC16 in the formation of multicellular aggregates remains to be defined. Here, we show that MUC16 alters E-cadherin cellular localization and expression. Consistent with this, MUC16 knockdown inhibited the formation of multicellular aggregates and, conversely, forced expression of MUC16 C-terminal domain (CTD) enhanced the formation of multicellular aggregates. MUC16 knockdown induces ß-catenin relocation from the cell membrane to the cytoplasm, decreases its expression by increasing degradation and decreases ß-catenin target gene expression. MUC16 CTD inhibits GSK-3ß-mediated phosphorylation and degradation of ß-catenin, leading to increased ß-catenin levels. Importantly, knockdown of ß-catenin inhibited multicellular aggregation. These findings indicate that MUC16 promotes the formation of multicellular aggregates by inhibiting ß-catenin degradation.

Transformation of NIH3T3 mouse fibroblast cells by MUC16 mucin (CA125) is driven by its cytoplasmic tail.

MUC16 (CA125) is a transmembrane mucin that contributes to the progression of epithelial ovarian cancer (EOC). Expression of MUC16 is not detectable in the epithelial surface of normal ovaries. MUC16 expression is, however, common in serous EOC as well as in metastatic and recurrent tumors. Despite these observations, its contribution to the development of EOC is unknown. We stably expressed either empty vector, MUC16 C-terminal domain (MUC16 CTD) or MUC16 TMU (a construct that lacks the cytoplasmic tail) in NIH3T3 mouse fibroblast cells. In this study, we provide evidence for the role of MUC16 CTD in oncogenic transformation. We show that ectopic expression of MUC16 CTD enhances the growth of NIH3T3 cells under normal and low serum conditions, and promotes anchorage-dependent colony formation. The deletion of the cytoplasmic tail abrogated these effects. MUC16 CTD expression in NIH3T3 cells also enhances the formation of colony in soft agar as compared to MUC16 TMU. MUC16 CTD expression enhances tumor formation in nude mice. Our findings provide the first evidence that MUC16 induces the transformation of NIH3T3 cells and indicate that MUC16 functions as an oncogene. Furthermore, our data suggest that the cytoplasmic tail is critical for MUC16 oncogenic properties.