Expression Patterns of the Genes Related to Neuronal Differentiation and Stratification of Patients' Prognosis in Stage 4 Neuroblastomas

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  • Stage 4神経芽腫における分化関連遺伝子(trk A, trk B, c-srcN2)の発現様式と予後層別化に関する検討
  • Stage4 シンケイ ガ シュ ニ オケル ブンカ カンレン イデンシ trkA trkB c srcN2 ノ ハツゲン ヨウシキ ト ヨゴソウ ベツカ ニ カンスル ケントウ

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Abstract

Purpose : The prognosis of the patients with stage 4 neuroblastomas found by clinical symptoms is very poor in spite of recent advances in multimodal treatment. We analyzed expression of genes related to neuronal differentiation in these tumors. Stratification of prognosis of such patients and future therapeutic approach are discussed in this paper. Materials and Methods : Genomic amplification of the N-myc gene was analyzed by Southern blot hybridization and expression of trk A, trk B, and src gene was analyzed by semi-quantitative RT-PCR in 24 clinically detected neuroblastomas at stage 4. Results : The patients having tumors with amplified N-myc, or low expression of trk A, or expression of trk B tended to die in a shorter period, but this tendency was not statistically significant. On the other hand, the tumors with high expression of c-srcN2 had significantly better prognosis. The tumors with amplified N-myc and expression of trk B were resistant to chemotherapy and most patients with those tumors died within 12 months after diagnosis. The prognosis of the patients having tumors with a single copy of N-myc and high expression of c-srcN2 was excellent, as they responded well to chemotherapy. There was a high rate of recurrence after complete remission in the tumors with amplified N-myc and no expression of trk B, and the tumors with a single copy of N-myc and low expression of c-srcN2. Conclusion : Analyses for amplification and expression of genes related to neuronal differentiation enabled stratification of the prognosis of the patients with stage 4 neuroblastomas. A new therapeutic approach is necessary against the tumors that are expected not to respond to chemotherapy or to recur after complete remission.

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