Integration of a bacterial gene sequence into a chronic eosinophilic leukemia patient's genome as part of a fusion gene linker

Saveen Sidhoo; Jesusa L Rosales; Ki-Young Lee

doi:10.1186/s40364-017-0101-z

Integration of a bacterial gene sequence into a chronic eosinophilic leukemia patient's genome as part of a fusion gene linker

Biomark Res. 2017 Jun 5:5:20. doi: 10.1186/s40364-017-0101-z. eCollection 2017.

Authors

Saveen Sidhoo¹, Jesusa L Rosales², Ki-Young Lee¹

Affiliations

¹ Arnie Charbonneau Cancer Institute, Departments of Cell Biology & Anatomy, University of Calgary, Calgary, AB T2N 4N1 Canada.
² Biochemistry & Molecular Biology, University of Calgary, Calgary, AB Canada.

Abstract

Analysis of databases from the human genome project (HGP), the 1000 Genomes Project (1KGP), and The Cancer Genome Atlas (TCGA) revealed bacterial DNA integration into the human somatic genome, particularly in tumor tissues. Fusion genes have also been associated with tumorigenesis and 34 PDGFR fusion genes are linked to hematological malignancies. Here, we determined that a 17-bp homologous sequence in Marinobacter sp. Hb8, Rhodococcus fascians D188, Rhodococcus sp. PBTS2, Micrococcus luteus strain trpE16 and M. luteus NCTC 2665 integrates into the genome of a chronic eosinophilic leukemia patient as part of the linker for the novel CDK5RAP2-PDGFRα fusion gene. The resulting fusion protein that has CDK5RAP2's self-activating domain and PDGFRa's tyrosine kinase domain but lacks PDGFRa's membrane-binding and ligand-dependent activation properties may act together with the integrated bacterial sequence to readily phosphorylate downstream targets, amplify proliferation signals and promote leukemic cancer progression.

Keywords: Cdk5rap2; Leukemia; PDGFRα.