Novel gene fusion discovery in Spitz tumours and its relevance in diagnostics

• Published in: Virchows Archiv : an international journal of pathology Vol. 485; no. 2; pp. 269 - 279
• Main Authors: Delsupehe, Louis, Steelandt, Thomas, Lemahieu, Julie, Volders, Pieter-Jan, Geerdens, Ellen, Berden, Severine, Daniels, Annick, Froyen, Guy, Maes, Brigitte
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-08-2024; Springer Nature B.V
• Subjects: Adolescent; Adult; Biomarkers, Tumor - genetics; Child; Diagnosis; Female; Fusion protein; Gene Fusion; Genomes; High-Throughput Nucleotide Sequencing; Histopathology; Humans; Hybridization; Kinases; Male; Medicine; Medicine & Public Health; Melanoma; Mutation; Neoplasms; Nevus, Epithelioid and Spindle Cell - diagnosis; Nevus, Epithelioid and Spindle Cell - genetics; Nevus, Epithelioid and Spindle Cell - pathology; Next-generation sequencing; Oncogene Proteins, Fusion - genetics; Oncology; Original Article; Pathology; Reverse transcription; Skin Neoplasms - diagnosis; Skin Neoplasms - genetics; Skin Neoplasms - pathology; Tumors; Young Adult; Spitz tumour; Dermatopathology; Spitz nevus; Gene fusion; Next-generation sequencing (NGS)
• ISSN: 0945-6317; 1432-2307; 1432-2307
• DOI: 10.1007/s00428-023-03649-9

In addition to morphologic analysis, molecular diagnostic work up of Spitz tumours is often of great value for their accurate diagnosis/classification. Nowadays, next-generation sequencing (NGS) is the predominant screening method in molecular diagnostics. Up to 80% of these melanocytic neoplasms comprise gene fusions as genetic anomalies for which the driver codes for a protein harbouring a kinase domain. However, because of the variety of fusion partners the use of PCR-based targeted enrichment NGS methods is not recommended. We describe a series of four Spitz tumour samples in which distinct gene fusions were detected by hybridisation-based capture NGS (
TPM3::ALK, LIMA1::ROS1, LRRFIP2::ROS1
and
MYO5A::RET
). Two of these fusions are not previously described. All 4 fusions were confirmed by reverse transcription-PCR. These findings demonstrate the need for molecular analysis that can detect unknown fusions in Spitz neoplasms for optimal diagnosis.