Identification of MET genomic amplification, protein expression and alternative splice isoforms in neuroblastomas
- Benedict Yan1,2,
- Malcolm Lim1,
- Lihan Zhou3,
- Chik Hong Kuick1,
- May Ying Leong1,
- Kol Jia Yong4,
- LeLe Aung5,
- Manuel Salto-Tellez2,4,6,
- Kenneth T E Chang1
- 1Department of Pathology and Laboratory Medicine, KK Women's and Children's Hospital, Singapore
- 2Department of Pathology, National University Health System and National University of Singapore, Singapore
- 3Department of Biochemistry, National University of Singapore, Singapore
- 4Cancer Science Institute, National University of Singapore, Singapore
- 5Department of Paediatric Medicine, KK Women's and Children's Hospital, Singapore
- 6Northern Ireland - Molecular Pathology Laboratory, Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, UK
- Correspondence to Professor Manuel Salto-Tellez, CCRCB, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7BL, UK; and Dr Kenneth T E Chang, Department of Pathology and Laboratory Medicine, KK Women's and Children's Hospital, Singapore, Singapore;
- Received 30 November 2012
- Revised 3 May 2013
- Accepted 26 May 2013
- Published Online First 25 June 2013
Background Crizotinib, a dual anaplastic lymphoma kinase (ALK) and mesenchymal-epithelial transition (MET) tyrosine kinase inhibitor, is currently being evaluated for the treatment of neuroblastoma. Its effects are thought to be mediated mainly via its activity against ALK. Although MET genomic/protein expression status might conceivably affect crizotinib efficacy, this issue has hitherto not received attention in neuroblastomas.
Aims/Methods MET genomic and protein expression status was characterised by silver in situ hybridisation and immunohistochemistry (IHC) respectively, in a cohort of 54 neuroblastoma samples. MET splice isoforms were characterised in 15 of these samples by quantitative PCR.
Results One case (1/54; prevalence 1.85%) displayed MET genomic amplification, while another case (1/54; prevalence 1.85%) displayed strong membranous MET protein expression (IHC score 3+). Alternative exon 10-deleted and exon 14-deleted MET splice isoforms were identified.
Conclusions MET amplification and protein expression, although low in prevalence, are present in neuroblastomas. This has implications when crizotinib is employed as a therapeutic agent in neuroblastomas. Additionally, the existence of alternatively spliced MET isoforms may have clinical and biological implications in neuroblastomas.