Department of Pathology, Hallym University Sacred Heart Hospital, Anyang, Republic of Korea.
Pathol Res Pract. 2011 Oct 15;207(10):634-9. doi: 10.1016/j.prp.2011.07.011. Epub 2011 Sep 21.
Neuroblastoma (NB) is one of the most common malignant pediatric tumors that show aggressive behavior. Most advanced-stage NBs have proven refractory to many treatment modalities, and a fundamental alternative therapy, such as inhibition of biological pathways, is now being explored. Anaplastic lymphoma kinase (ALK) has recently been identified as an activation mutation in familial or high-risk sporadic NBs. We examined the prevalence of the ALK mutation in 54 NB cases (23 pre-treatment cases and 31 cases for which specimens were available before and after treatment) and the presence of the ALK mutation in various pediatric tumors. We detected the ALK mutation (F1174C and R1275Q) in 2 (3.7%) of the 54 NB specimens. Both cases showed poorly differentiated and advanced-stage NBs. No ALK mutations were detected in other pediatric tumors. The frequency of the ALK mutation was somewhat lower than that expected in Korean patients with NBs. The mutation detected in the present study was one of the hotspot mutations, including positions of F1174 and R1275 reported previously. The results of the present study suggest the possibility of potential roles of ALK inhibitors in the therapeutics of a small population of neuroblastoma carrying mutated ALK kinases.
神经母细胞瘤（NB）是最常见的儿童恶性肿瘤之一，具有侵袭性行为。大多数晚期 NB 对许多治疗方法都有抗药性，目前正在探索一种基本的替代治疗方法，如抑制生物途径。间变性淋巴瘤激酶（ALK）最近被确定为家族性或高危散发性 NB 的激活突变。我们检测了 54 例 NB 病例（23 例治疗前病例和 31 例治疗前和治疗后标本可用的病例）中 ALK 突变的发生率以及各种儿科肿瘤中 ALK 突变的存在。我们在 2 例（3.7%）54 例 NB 标本中检测到 ALK 突变（F1174C 和 R1275Q）。这两个病例均表现为低分化和晚期 NB。在其他儿科肿瘤中未检测到 ALK 突变。ALK 突变的频率略低于韩国 NB 患者的预期。本研究中检测到的突变是先前报道的 F1174 和 R1275 位置等热点突变之一。本研究的结果表明，ALK 抑制剂在携带突变 ALK 激酶的一小部分神经母细胞瘤治疗中可能具有潜在作用。
