A Pilot Study on ALK Gene Mutations in Neuroblastoma

Neuroblastoma (NB) originates from the sympathetic nervous system and is one of the most common cancers in infants and children. In our hospital, nearly 70% of patients are diagnosed with stage 4, metastatic disease with a poor prognosis, despite the use of multimodal therapy including chemotherapy, surgery, autologous stem cell transplantation, radiation therapy, and differentiation therapy. To improve the survival rate and patient care, our NB Study Group has devoted to the research on NB-specific molecular imaging, biomarkers, and target therapy. We have confirmed studies in cancer genetics by showing that N-myc gene (MYCN) amplification and segmental abnormalities on overall genomic profiling both have an adverse effect on treatment outcome. Therefore, there is an unmet need for the development of novel molecular target therapy in NB. Recently, the anaplastic lymphoma kinase (ALK) oncogene has been found to play an important role in the pathogenesis of NB, as well as serving as the driver mutations in approximately 10% of high-risk NB. The availability of ALK inhibitors also enables ALK as a treatment target in NB. In this proposal, we plan to utilize gene sequencing, array-comparative hybridization, and multiplex ligation-dependent probe amplification methods to evaluate the frequencies and characteristics of ALK mutations and amplifications in patients with NB. The gene and protein expression of ALK will also be evaluated by quantitative polymerase chain reaction(PCR) and immunohistochemistry, respectively, and compared with ALK genotype. The overall genomic pattern, clinical characteristics, histopathology, and treatment outcome of ALK-mutated NB patients will be analyzed. The results from this study may serve as the first report on ALK mutations of NB in Taiwan and will be used for the development of standardized genetic diagnosis protocols, as well as the design of future clinical trials targeting ALK.

Sex

All

Maximum age

50 Years

Inclusion Criteria:

1. Diagnosed by clinical criteria(one of below)

   Proved or maybe as Neuroblastoma by :
   1. pathological section
   2. Bone meta with 24 hrs urine Vanillylmandelic acid(VMA)or Homovanillic acid(HVA) elevated
   3. CT or MRI found tumor around adrenal gland or Neuroblastic tumor
2. Have tumor or blood samples to analyze ALK gene：

   1. will operation to remove tumor or biopsy, and will preserve tumor sample；or
   2. after operation and have tumor sample preserved；or
   3. after operation without tumor sample, but agree to take blood sample to analyze ALK mutation
3. Signed Inform Consent Form

Exclusion Criteria:

(1) After informed but still not consent