Novel activating SNRNP70-ALK fusion in congenital infant-type hemispheric glioma displays clinical response to lorlatinib: a case-report
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.
Authors
- Ruth H. Palmer (ORCID: https://orcid.org/0000-0002-2735-8470)
- Richard W. Rosenquist (ORCID: https://orcid.org/0000-0002-9067-9058)
- Blaž Oder (ORCID: https://orcid.org/0000-0001-7984-3104)
- Jesper Eisfeldt (ORCID: https://orcid.org/0000-0003-3716-4917)
- Teresita Díaz de Ståhl (ORCID: https://orcid.org/0000-0001-5933-6623)
- Johanna Sandgren (ORCID: https://orcid.org/0000-0001-6776-2649)
- Kleopatra Georgantzi (ORCID: https://orcid.org/0000-0001-9304-6144)
- Christopher Illies (ORCID: https://orcid.org/0000-0002-1488-0294)
- Cecilia Arthur (ORCID: https://orcid.org/0000-0002-0645-6530)
- Cecilia Jylhä (ORCID: https://orcid.org/0000-0002-6964-2517)
- Daniel Hägerstrand (ORCID: https://orcid.org/0000-0001-7270-0776)
- Ulrika Sandvik (ORCID: https://orcid.org/0000-0002-9273-2158)
- J Svoboda (ORCID: https://orcid.org/0009-0006-5546-1017)
- Gisela Barbany
- Emma Tham
- Bengt Hallberg
- Jikui Guan
Institutions
- Karolinska University Hospital (SE)
- Karolinska Institutet (SE)
- University of Gothenburg (SE)
Publication Details
- Journal
- npj Precision Oncology
- Published
- 2026-02-26
- DOI
- https://doi.org/10.1038/s41698-026-01336-x
- Primary Topic
- Glioma Diagnosis and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Cancerfonden
- Knut och Alice Wallenbergs Stiftelse
- Vetenskapsrådet
- Barncancerfonden
- Science for Life Laboratory
- Uppsala Multidisciplinary Center for Advanced Computational Science