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

Cecilia Arthur, Kleopatra Georgantzi, Teresita Díaz de Ståhl, Jikui Guan, Blaz Oder, Cecilia Jylhä, Christopher Illies, Johanna Sandgren, Jan Svoboda, Jesper Eisfeldt, Gisela Barbany, Richard Rosenquist, Ulrika Sandvik, Daniel Hägerstrand, Bengt Hallberg, Ruth Palmer, Emma Tham
NPJ Precis Oncol. 2026 Feb 26;10(1):113. doi: 10.1038/s41698-026-01336-x.

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.