Developmental origins shape the paediatric cancer genome

Area of Science:

• Genomics
• Oncology
• Molecular Biology

Background:

• Paediatric cancer genomes possess distinct characteristics compared to adult cancers.
• Technological advancements have provided unprecedented insights into these genomic differences over the past two decades.
• Paediatric cancers arise from developing tissues and often exhibit low mutation burdens.

Purpose of the Study:

• To review recent findings on paediatric cancer genomics from a pan-cancer perspective.
• To highlight the distinct genomic features of paediatric cancers, including transcriptional and regulatory alterations.
• To provide an outlook on future investigations and therapeutic strategies.

Main Methods:

• Review of recent findings in paediatric cancer genomics.
• Analysis of genome-wide genetic screening data.
• Pan-cancer perspective on distinct paediatric cancer characteristics.

Main Results:

• Paediatric cancers are characterized by low mutation burden and are driven by variants affecting transcriptional activity, chromatin state, and non-coding regulatory regions.
• Tumours comprise multiple cell populations with traceable lineages to fetal origins.
• Genome-wide screening identified vulnerabilities linked to cell of origin and transcription deregulation.

Conclusions:

• Genomic insights into paediatric cancer are crucial for developing novel therapeutic approaches.
• New therapies, including small molecules, immunotherapy, and targeted protein degradation, can be designed based on identified vulnerabilities.
• Further investigations are needed to fully understand and target paediatric cancer biology.