Partial deletion of the ALK gene in ALK-positive anaplastic large cell lymphoma.

Abstract

Anaplastic lymphoma kinase (ALK) protein is an orphan receptor tyrosine kinase that is constitutively activated by aberrant translocations of the ALK gene in anaplastic large cell lymphoma, ALK-positive and several other cancers. Additionally, aberrant mutation and amplification of the ALK gene, resulting in ALK kinase activation, were detected mainly in neuroblastoma. Recently, truncated ALK protein was also reported in neuroblastoma. Here, we describe a novel truncated form of the ALK transcript with in-frame skipping through exons 2 to 17 (ALKΔ2-17) in anaplastic large cell lymphoma, ALK-positive. The ALKΔ2-17 showed ligand-independent deregulated phosphorylation that initiated strong STAT3 signalling in NIH3T3 cells. The ALKΔ2-17-transduced NIH3T3 cells showed oncogenic potential in a colony formation assay. Our data indicate that the aberrant deletion of the ALK gene might be oncogenic, providing a novel insight into the oncogenic role of the ALK pathway.

• Authors: Suguru Fukuhara, Junko Nomoto, Sung-Won Kim, Hirokazu Taniguchi, Akiko Miyagi Maeshima, Kensei Tobinai, Yukio Kobayashi
• Journal: Hematological oncology (Hematol Oncol) Vol. 36 Issue 1 Pg. 150-158 (Feb 2018) ISSN: 1099-1069 [Electronic] England
• PMID: 28665006 (Publication Type: Case Reports, Journal Article)
• Copyright: Copyright © 2017 John Wiley & Sons, Ltd.

Chemical References

• ALK protein, human
• Alk protein, mouse
• Anaplastic Lymphoma Kinase
• Receptor Protein-Tyrosine Kinases

Topics

• Anaplastic Lymphoma Kinase
• Animals
• Cell Line, Tumor
• Humans
• Lymphoma, Large-Cell, Anaplastic (enzymology, genetics)
• Mice
• Middle Aged
• Mutation
• NIH 3T3 Cells
• Receptor Protein-Tyrosine Kinases (metabolism)