Neuroblastoma

Abstract

Neuroblastoma is one of the most common solid tumors in children and has a diverse clinical behavior that largely depends on the tumor biology. Neuroblastoma exhibits unique features, such as early age of onset, high frequency of metastatic disease at diagnosis in patients over 1 year of age and the tendency for spontaneous regression of tumors in infants. The high-risk tumors frequently have amplification of the MYCN oncogene as well as segmental chromosome alterations with poor survival. Recent advanced genomic sequencing technology has revealed that mutation of ALK, which is present in ~10% of primary tumors, often causes familial neuroblastoma with germline mutation. However, the frequency of gene mutations is relatively small and other aberrations, such as epigenetic abnormalities, have also been proposed. The risk-stratified therapy was introduced by the Japan Neuroblastoma Study Group (JNBSG), which is now moving to the Neuroblastoma Committee of Japan Children's Cancer Group (JCCG). Several clinical studies have facilitated the reduction of therapy for children with low-risk neuroblastoma disease and the significant improvement of cure rates for patients with intermediate-risk as well as high-risk disease. Therapy for patients with high-risk disease includes intensive induction chemotherapy and myeloablative chemotherapy, followed by the treatment of minimal residual disease using differentiation therapy and immunotherapy. The JCCG aims for better cures and long-term quality of life for children with cancer by facilitating new approaches targeting novel driver proteins, genetic pathways and the tumor microenvironment.

The prognostic roles of and correlation betweenALKandMYCNprotein expression in neuroblastoma

“…While MYCN resides within this locus, no mutations were found on MYCN gene. Instead, germline mutations in the ALK gene had been identified as the leading cause of familial neuroblastoma,15 16 and these mutations were also somatically acquired in sporadic neuroblastoma 13 14 18 32 33. These findings in familial or sporadic neuroblastoma suggest that, in addition to MYCN , ALK is also an oncogenic driver in neuroblastoma 34.…”

MicroRNA-145 overexpression inhibits neuroblastoma tumorigenesis in vitro and in vivo

“…Treatment strategies for high-risk disease include high-dose chemotherapy [3], surgery [4], radiotherapy [5], anti-GD2 immunotherapy [6] and targeting therapy [7,8]. Despite recent FDA approval of anti-GD2 antibody-based immunotherapy for highrisk NB patients in first remission, the cure rates remain less than 50% accompanied by significant morbidity in survivors [9].…”

PPP3CB contributes to poor prognosis through activating nuclear factor of activated T‐cells signaling in neuroblastoma

“…MYCN oncogene amplification as well as chromosome 1p and 11q losses are hallmarks of aggressive NBs. In addition, the anaplastic lymphoma kinase ( ALK ) oncogene is mutated or amplified in a subset of sporadic NBs with unfavorable prognosis . However, these genomic and genetic aberrations only account for a small portion of aggressive NBs.…”

“…However, these genomic and genetic aberrations only account for a small portion of aggressive NBs. MYCN amplification is found in approximately 20% of NB patients, while ALK amplification and mutation are reported to occur in approximately 3‐5% and 6‐12% of primary NBs, respectively . Several independent groups have recently conducted whole‐genome or whole‐exome sequencing on NB patients .…”