Seek and Ye Shall Find: Subclonal Anaplastic Lymphoma Kinase Mutations

Abstract

Bellini and colleagues demonstrate the importance of next-generation sequencing to uncover subclonal anaplastic lymphoma kinase (ALK) mutations in neuroblastoma. Although the significance of these subclonal aberrations is not yet understood, deep sequencing could identify patients whose tumors may respond to ALK inhibitors.

Figure 1. Possible origins of ALK mutations detected at relapse

A, ALK-mutated cells can be clonal and form the dominant transformed population. These mutations can be identified through conventional sequencing methods. At relapse, these clonal populations retain their dominance, although the possibility of their replacement by clones bearing new mutations cannot be excluded. B, ALK-mutated cells are subclonal at diagnosis, and could either be eradicated or evolve and expand at relapse to form the dominant transformed population. These mutations at diagnosis can be missed through conventional sequencing and will need to be searched for through advanced sequencing techniques. C, tumors without ALK mutations at diagnosis but in which ALK mutations arise de novo at relapse.