Methodology:

Prospective, multicentric, open, non-randomised, non-therapeutic, interventional study

To identify and characterise:

• meaningful molecular genetic alterations,
• meaningful immunological features of high risk childhood, adolescents and young adult cancers, at diagnosis, during patient treatment and follow-up (time dimension).

Inclusion Criteria:

1. Inclusion within 3 months after diagnosis

2. Availability of a cryopreserved tumour sample (primary and/or metastatic and/or lymph nodes) or peripheral blood or bone marrow samples (if invasion more than 30% of lymphoblasts) for leukaemias, obtained at the time of diagnosis during a routine procedure

3. Availability of a formalin-fixed paraffin-embedded (FFPE) tumour sample (primary and/or metastasis and/or lymph nodes), obtained at the time of diagnosis during a routine procedure (except for leukaemia patients)

4. Age: ≤ 25 years at diagnosis

5. Written patient informed consent, or parents or legal representative written informed consent and assent of the child and the adolescent

6. Compulsory affiliation to a social security scheme

   Additional inclusion criteria for the study:

   To avoid multiple sampling for children, adolescents and young adults with cancer, patients already included or to be included in a study with similar analyses and/or objectives might also be included in MICCHADO study and in this case, samples or data might be exchanged on a collaborative basis.

   Cohort 1:

   • High risk neuroblastoma:

     - Any type of neuroblastoma with MYCN amplification, except INSS stage 1

     - Stage 4 neuroblastoma in children older than one year at diagnosis

   • High risk rhabdomyosarcoma:

     • Foxo1 rearrangement any stage;
     • and / or N1 ;
     • and / or metastatic rhabdomyosarcoma

   • High risk Ewing sarcoma:

     • Metastatic Ewing sarcoma family of tumours (ESFT)
     • Localised inoperable Ewing sarcoma with primary tumours ≥ 200 ml

   • High risk osteosarcoma:

     - Metastatic osteosarcoma

     - Localised inoperable osteosarcoma

   • High risk leukaemia:

     • Secondary acute myeloid leukaemia
     • Biphenotypic acute leukaemia

   Cohort 2:

   • Extra cerebral or cerebral high risk tumours including:

   • other metastatic sarcomas,
   • other rare high risk cancers,
   • high risk renal tumours with surgery after an initial chemotherapy
   • rhabdoid brain tumours (AT/RT) and extra cerebral rhabdoid tumours
   • high risk or metastatic cancers of unclear histological diagnosis • Lymphoblastic leukaemia with high MRD at Day 78 (time point 2) • Very high risk T-cells acute lymphoblastic leukaemia:
   • MRD ≥ 10-2 at the end of the induction ;
   • or MRD ≥ 10-3 at Day 78

   Cohort 3:

   Children, adolescents and young adults, with low/intermediate risk cancers belonging to the following types:

   • Neuroblastoma:

   - Localised, without MYCN amplification

   • Localised, INSS stage 1, with MYCN amplification

   • Stage 4s, in infants (younger than one year at diagnosis), without MYCN amplification

     • Rhabdomyosarcoma:

   • Localised, without Foxo1 rearrangement

     • ESFT:

   • All non-high risk localised ESFT • Osteosarcoma:

   • All non-high risk localised osteosarcoma

   Exclusion Criteria:

   Main non-inclusion Criteria common to all study cohorts:

1) Age: patients > 25 years old at diagnosis 2) Absence of patient or parents or legal representative written informed consent 3) Patient for whom follow-up by the investigating centre does not appear feasible