# Novel activating SNRNP70-ALK fusion in congenital infant-type hemispheric glioma displays clinical response to lorlatinib: a case-report

## TL;DR

A child with a brain tumor showed partial regression after treatment with lorlatinib following discovery of a new SNRNP70-ALK fusion through multi-omics analysis.

## Contribution

A novel SNRNP70-ALK fusion was identified as a therapeutic target in infant-type hemispheric glioma, responding to lorlatinib treatment.

## Key findings

- A novel SNRNP70::ALK fusion was identified in a congenital infant-type hemispheric glioma.
- Lorlatinib treatment led to sustained partial tumor regression and no new neurological symptoms after two years.
- Functional studies confirmed the fusion protein is expressed and active in the patient’s tumor.

## Abstract

We report a child with an antenatally detected brain tumor that progressed over three years’ time despite surgery, chemo- and proton therapy. Retrospective whole-genome and transcriptome sequencing with methylation analysis of primary tumor tissue led to the molecular diagnosis infant-type hemispheric glioma, and identified a novel SNRNP70::ALK fusion, providing a therapeutic target for compassionate-use precision treatment with the ALK tyrosine kinase inhibitor lorlatinib. Functional studies confirmed the fusion protein to be expressed and active in the patient’s tumor. After two years of therapy, the child has sustained partial tumor regression on MRI and no new neurological symptoms. We conclude that comprehensive multi-omics analyses are required for correct molecular diagnosis in childhood CNS tumors and can radically impact patient outcome by identifying molecular targets for precision treatment.