Immunohistochemistry for ATRX Can Miss ATRX Mutations: Lessons From Neuroblastoma.

摘要: Neuroblastoma is the most common extracranial solid tumor of childhood with a median age presentation 17 months. A theme in high-risk neuroblastoma maintenance telomeres, one mechanism for which involves alternate lengthening telomeres (ALT) associated ATRX gene mutations. Mutations are believed to result loss protein, and therefore immunohistochemistry used detect We screened 133 cases by immunohistochemistry, found 9 partial total absence ATRX. Sequencing mutations detected mutation 1 cases, suggesting immunostaining was not reliable detecting To correlate ALT, fluorescence situ hybridization (FISH) ALT performed 6 these 5 (from 4 patients) showed implying impaired protein function, despite failure identify mutation. Two other large deletions diffusely positive staining but FISH. Four patients ALT-positive tumors were over years old. Therefore, 29 additional old above ATRX-positive FISH detected, bringing 29% (10/34) children above, 70% immunohistochemistry. Patients tend have more chronic progressive course disease. Screening at diagnosis may help who might benefit from personalized therapy directed against ALT. However, relaying on negative miss significant proportion patients. The addition as part diagnostic workup, especially older (5 y above), would ensure that correctly identified anti-ALT therapy.