Gray Zone Lymphoma Arising in the Neck of a Teenager With a Germline Mutation in TP53

Gatineau-Sailliant, Sophie; Turcotte, Karine; Quintal, Marie-Claude; Turpin, Sophie; Champagne, Josette; Petrella, Tony; Roussy, Mathieu; Cellot, Sonia; Soglio, Dorothée Bouron‐Dal

doi:10.1097/mph.0000000000001308

Cited by 1 publication

(1 citation statement)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Up to 10% of pediatric patients with cancer are estimated to carry an underlying hereditary cancer predisposition gene, 37 making the discovery of clinically relevant germline variants 38 inevitable during NGS analysis using germline SNVs to distinguish cancer-specific somatic mutations from constitutional variants. In the TRICEPS study, we detected pathogenic or likely pathogenic germline variants in 8 patients (13%), and this information was reported to the referring clinician.…”

Section: Discussionmentioning

confidence: 99%

Molecular Profiling of Hard-to-Treat Childhood and Adolescent Cancers

et al. 2019

Self Cite

View full text Add to dashboard Cite

IMPORTANCE Little progress in pediatric cancer treatment has been noted in the past decade, urging the development of novel therapeutic strategies for adolescents and children with hard-totreat cancers. Use of comprehensive molecular profiling in the clinical management of children and adolescents with cancer appears a suitable approach to improve patient care and outcomes, particularly for hard-to-treat cases. OBJECTIVE To assess the feasibility of identifying potentially actionable mutations using nextgeneration sequencing-based assays in a clinically relevant time frame. DESIGN, SETTING, AND PARTICIPANTS This diagnostic study reports the results of the TRICEPS study, a prospective genome sequencing study conducted in Québec, Canada. Participants, aged 18 years or younger at diagnosis, with refractory or relapsed childhood and adolescent cancers were enrolled from April 2014 through January 2018. Whole-exome sequencing (WES) of matched tumor normal samples and RNA sequencing of tumor were performed to identify single-nucleotide variants, fusion transcripts, differential gene expression, and copy number alterations. Results reviewed by a team of experts were further annotated, synthesized into a report, and subsequently discussed in a multidisciplinary molecular tumor board. MAIN OUTCOMES AND MEASURES Molecular profiling of pediatric patients with hard-to-treat cancer, identification of actionable and targetable alteration needed for the management of these patients, and proposition of targeted and personalized novel therapeutic strategies. RESULTS A total of 84 patients with hard-to-treat cancers were included in the analysis. These patients had a mean (range) age of 10.1 (1-21) years and a similar proportion of male (45 [54%]) and female (39 [46%]). Sixty-two patients (74%) had suitable tissues for multimodal molecular profiling (WES and RNA sequencing). The process from DNA or RNA isolation to genomic sequencing and data analysis steps took a median (range) of 24 (4-41) days. Potentially actionable alterations were identified in 54 of 62 patients (87%). Actions were taken in 22 of 54 patients (41%), and 18 (33%) either were on a second or third line of treatment, were in remission, or had stable disease and thus no actions were taken. CONCLUSIONS AND RELEVANCE Incorporating genomic sequencing into the management of hard-to-treat childhood and adolescent cancers appeared feasible; molecular profiling may enable the identification of potentially actionable alterations with clinical implications for most patients, (continued) Key Points Question Can genome sequencing facilitate the molecular profiling of the patient's tumor to identify actionable and targetable alterations? Findings In this diagnostic study of 62 consecutive pediatric patients with hard-to-treat cancer who were enrolled in the TRICEPS study, incorporating multimodal genomic sequencing, including RNA sequencing, into the management of refractory or relapsed childhood and adolescent cancers identified potentially actionable alterations in 54 (87%)...

show abstract

Section: Discussionmentioning

confidence: 99%