In the light of the development of high-throughput technologies enabling a biology-based reclassification of tumors and the increasing number of available specifically targeting anticancer agents the era of "precision medicine" has begun. Several clinical precision medicine trials with the aim of stratifying treatment according to molecular profiles (for example in France: 'MOlecular Screening for CAncer Treatment Optimization' MOSCATO-01, SHIVA, PROFILER, Safir01, Safir02) are ongoing in adults and have shown the feasibility of this approach. MOSCATO-01 is the first trial worldwide including pediatric patients, performing an on-purpose intervention and molecular profiling in recurrent tumors. Together with more than 500 adult patients, between December 2012 to August 2014, the tumors of 35 children and adolescents have been profiled, confirming that this approach is feasible in pediatric patients albeit with accelerated time stringencies. Importantly, the results of the first children and adolescents profiled showed that 2/3 of patients had 'actionable' alterations using hot spot mutations sequencing and CGH array (Geoerger B et al, ASCO 2014).

The project 'MAPPYACTS' will use both Whole Exome Sequencing (WES) and RNA Sequencing of tumor tissue to increase the number of targetable genomic alterations. Furthermore to improve understanding of the overall molecular profile and possible response to treatment, methylation array, miRNA expression profiles, and study of immunomodulators will be performed on tumor samples subsequently. CLIP2 (INCa-labeled early phase clinical trials centers) - SiRIC (INCa- labeled comprehensive cancer centers) molecular profiling and bioinformatics platforms will contribute with their expertise in molecular profiling projects and characterization of pediatric cancers. Data interpretation of molecular genetic alterations detected by WES and RNA Seq and treatment recommendation will be done within a multidisciplinary therapeutic molecular biology tumor board.

'MAPPYACTS' will produce one of the largest cohorts of molecularly characterized relapsed tumors reported to date, and thanks to increased access to clinical trials since the European pediatric legislation, the investigators expect that 20-30% of patients can be stratified into a targeted trial based on the detected profile.

It is the investigators' intention that this initiative paves the way to enrich ongoing clinical targeted agent trials, to increase the numbers of stratified clinical trials, to an earlier access to targeted agents, and will play a crucial role in the relevant development of these new agents in pediatric malignancies.

Inclusion criteria:

• Written informed consent signed by the patient, or parents or legal representative and assent of the minor child to perform biopsy/surgical resection/aspiral/sample and molecular analysis of the tumor and blood sample
• Patient with confirmed solid tumor or leukemia which is recurrent or refractory to standard treatment and who is eligible for an early phase clinical trial
• In case of solid tumor, lesion must be accessible for biopsy or surgical resection or cytological puncture
• Age: Patients aged ≥ 6 months at time of inclusion and aged ≤ 18 years at the time of initial diagnosis
• Performance status and life expectancy that allows treatment in an experimental trial: Karnofsky performance status ≥ 70% for patients > 12 years of age, Lansky play scale ≥ 70% for patients ≤ 12 years of age
• Adequate organ function:

Adequate hematopoietic function for patients with solid tumor (Leukemia patients are excluded from hematological criteria) : Neutrophils >1.0 x 109/l, Platelets >100 x 109/l, Heamoglobin >80 g/l (transfusion allowed) In case of bone marrow involvment: Neutrophils >/= 0.75 x 109/l (unsupported) , Platelet count >/= 0.75 x 109/l (unsupported) Adequate hepatic function: ALAT/ASAT <2.5 x ULN, Bilirubin ≤1.5 x ULN (in case of tumor involvement of the liver ALAT/ASAT <5 x ULN) Adequate renal function: Serum creatinemia <1.5 x ULN for age. In case serum creatinine >1.5 ULN according to age, creatinine clearance has to be >70mL/mL/1.73 m2 or glomerular filtration rate measurement >70% of the expected value

- Patients affiliated to a Social Security Regimen or beneficiary of the same as per local regulatory requirements

Exclusion criteria:

• Life expectancy ≤ 3 months
• Symptomatic CNS metastases
• In case of leukemia, are excluded patients with isolated meningitis relapses.
• Coagulation disorder that prevents the accomplishment of a biopsy or surgery
• Uncontrolled infections not responsive to antibiotics, antiviral medicines, or antifungal medicines
• Presence of ≥ CTCAE grade 2 toxicity (except alopecia, ototoxicity, lymphopenia which are not excluded if grade 3 or less) due to prior cancer therapy
• Malignant disease other than that being treated in this study. Exceptions to this exclusion include the following: malignancies that were treated curatively and have not recurred within 3 years prior to study entry
• Any concurrent illness or laboratory abnormality that in opinion of investigator may interfere with the interpretation of study results, may suppose a risk for the realization of biopsy/surgery, and in the judgment of the investigator would make the patient inappropriate for the study
• Evidence of active viral Hepatitis B or C or known diagnosis of human immunodeficiency virus infection