APOBEC3B expression in human leptomeninges and meningiomas

Abstract

Abstract. Nucleic acid-editing enzymes of the apolipoprotein B mRNA-editing enzyme (APOBEC) family have been associated with somatic mutation in cancer. However, the role of APOBEC catalytic subunit 3B (APOBEC3B) editing in the pathogenesis of base substitutions in meningiomas is unknown. In the present study, the expression of APOBEC3B was examined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analyses in five fetal and one adult human leptomeninges and 38 meningiomas. Genomic DNA was sequenced using the Illumina Tru-Seq Cancer Panel. Three meningioma primary cultures were also established and treated with cerebrospinal fluid form patients without neurological disease or platelet-derived growth factor-BB (PDGF-BB), prior to evaluation of APOBEC3B expression. By western blotting, APOBEC3B was revealed to be present in 100% of the fetal leptomeninges, and in 88% of World Health Organization grade I, 100% of grade II and 83% of grade III meningiomas tested, but was not different between grades. RT-qPCR revealed no difference in the mRNA expression of APOBEC3B between grades. Sequencing revealed no elevated levels of the C>T mutations that are characteristic of APOBEC3B editing of genomic DNA. Treatment with cerebrospinal fluid and PDGF-BB had no effect on APOBEC3B protein expression in the leptomeningeal or meningioma cells. These findings suggest that the mutations associated with increased APOBEC3B expression may not be central to the pathogenesis of meningiomas. IntroductionRecent studies have indicated that normal cellular enzymatic activity may contribute to the genomic changes associated with various neoplasias (1-3). Apolipoprotein B mRNA-editing enzymes (APOBEC) comprise a family of enzymes that protect immune function and are involved in mRNA editing; their cytosine deaminase activity may also induce base substitutions in the genomes of malignancies (1,2).APOBEC3B is a cytosine deaminase that is responsible for the deamination of cytosines in the genome of host cells, producing cytosine to thymidine mutations (2). Recently studies have found that APOBEC3B is overexpressed in several types of malignancy, resulting in clusters of C>T mutations that are considered to be the signature of APOBEC mutation in tumors. Analysis of whole-genome and whole-exome sequencing data from various types of malignancy have implicated APOBEC members in mRNA editing and the production of cytosine mutation clusters in the development or progression of numerous neoplastic processes, encompassing lung, breast, hepatic and hematopoietic malignancies (4-9). APOBEC3B overexpression has been identified in breast, head and neck cancers (7-10). Although APOBEC3B expression has not been studied in meningiomas, the presence of C>T point mutations in some meningioma cases raises the possibility that APOBEC3B may participate in the pathogenesis of at least a subset of meningiomas (11).The present study evaluated APOBEC3B expression in addition to mutations in a series of normal leptomeninges, an...

APOBEC3B is expressed in human glioma, and influences cell proliferation and temozolomide resistance

“…In the present study, it was demonstrated that APOBEC3B, a member of the APOBEC family, was overexpressed in glioblastoma (WHO grade IV), and was identified in astrocytic tumor regions and nearby tumor vessels. To date, APOBEC3B has only been detected in human leptomeninges and meningioma, to the best of our knowledge (17). However, Talagas et al (18) reported that certain oligodendroglial intracranial tumors that do not exhibit 1p/19q deletions are characterized by various other mutations, including a homozygous deletion at 22q13.1 (APOBEC3B gene).…”