Molecular-cytogenetic studies of PVT1 rearrangements in hematological malignancies

2015 Fiscal Year Final Research Report

• Project/Area Number: 25461432
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Taniwaki Masafumi 京都府立医科大学, 医学(系)研究科(研究院), 教授 (80163640)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: PVT1遺伝子 / キメラmRNA / 遺伝子増幅 / 骨髄性白血病 / NSMCE2 / クロモスリプシス

Outline of Final Research Achievements

Specific chromosomal translocations in hematological malignancies are a clue of identifying rearranged gene at the region of breakpoints. To gain insight into the role(s) of dmins, we cytogenetically and molecularly analyzed 8q24 amplicons in acute myelogenous leukemia (AML) patient-derived leukemic cells and AML-derived cell line (HL60), identifying fusion transcripts between PVT1 exon 1a and NSMCE2 exon 3 in the patient, and a fusion gene between exon 6 of NSMCE2 and exon 1 of BF104016, a noncoding RNA sharing the sequence of CCDC26 exon 4. These novel chimeric RNAs, PVT1-NSMCE2 and CCDC26-NSMCE2, were identified in association with dmins showing 8q24 amplicons. Chromothripsis is a possible cytogenetic mechanism of generating these novel chimeric genes. PVT1 and CCDC26 are long intergenic non-coding RNAs (lincRNAs). Our study suggests that the fusion genes involving lincRNAs potentially plays as-yet-unknown oncogenic functional roles.

Free Research Field

血液内科学