• Subjects must have proven pediatric cancer with confirmation at diagnosis or at the time of recurrence/progression and clinical determination of disease for which there is no known effective curative therapy or disease that is refractory to established proven therapies fitting into one of the following categories:

• Disease Status:

‣ High Risk Neuroblastoma-

⁃ Patients that have relapsed following standard of care therapy or having progressed during standard of care therapy and non-responsive/progressive to accepted curative chemotherapy.

⁃ Neuroblastoma must be age \>12 months at enrollment

‣ Diffuse Intrinsic Pontine (or other brain stem) Glioma

⁃ Newly-diagnosed patients willing to undergo biopsy

⁃ Must be within 2 months of diagnosis and prior to starting radiation

⁃ DIPG must be ≥ 3 years of age at enrollment

∙ All subjects must be age ≤ 30 years at enrollment

‣ Patient and/or parents/guardian willing to consent to biopsy for obtaining tumor material for confirmatory diagnosis and/or tumor RNA extraction and amplification.

‣ Subjects must have measurable disease as defined Per section 8 at the time of biopsy and tumor must be accessible for biopsy. Tumor samples submitted for analysis must contain \>30% viable tumor tissue to qualify. In addition, subjects with NB disease confined to the bone marrow are eligible to enroll if the degree of marrow involvement is expected to be \>30%.

‣ Current disease state must be one for which there is currently no known effective therapy

‣ Specimens will be obtained only in a non-significant risk manner and not solely for the purpose of investigational testing.

‣ Lansky or Karnofsky Score must be ≥ 60

‣ Bone Marrow:

⁃ ANC (Absolute neutrophil count) ≥ 1000/µl (unsupported)

• Platelets ≥ 100,000/µl (can be transfused)

• Hemoglobin \> 8 g/dL (can be transfused)

‣ Renal: Serum creatinine ≤ upper limit of institutional normal.

‣ Adequate liver function must be demonstrated, defined as:

⁃ Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age AND

• ALT (SGPT) ≤ 3 times upper limit of normal (ULN) for age

• AST (SGOT) ≤ 3 times upper limit of normal (ULN) for age.

‣ Subjects with CNS disease currently taking steroids must have been on a stable dose of steroids for at least one week prior to their biopsy and must not have progressive hydrocephalus at enrollment.

‣ A negative serum pregnancy test is required for female participants of childbearing potential (≥13 years of age or after onset of menses)

‣ Both male and female post-pubertal study subjects need to agree to use one of the more effective birth control methods during treatment and for six months after treatment is stopped. These methods include total abstinence (no sex), oral contraceptives (the pill), an intrauterine device (IUD), levonorgestrel implants (Norplant), or medroxyprogesterone acetate injections (Depo-provera shots). If one of these cannot be used, contraceptive foam with a condom is recommended.

‣ Informed Consent: All subjects and/or legal guardians must sign informed written consent. Assent, when appropriate, will be obtained according to institutional guidelines

‣ Post-Biopsy: Patients with post-biopsy neurological deficits should have deficits that are stable for a minimum of 1 week prior to registration.