Biological Characterisation of High Risk CHildhood Cancer in Children, Adolescents and Young Adults (MICCHADO)

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

• Inclusion within 3 months after diagnosis
• 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
• 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)
• Age: ≤ 25 years at diagnosis
• Written patient informed consent, or parents or legal representative written informed consent and assent of the child and the adolescent
• 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:

• 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