In vivo Engineering of Chromosome 19 q-arm by Employing the CRISPR/AsCpf1 and ddAsCpf1 Systems in Human Malignant Gliomas (Hypothesis).

Abstract

Deletions of the q13.3 region of chromosome 19 have been found commonly in all three main kinds of diffuse human malignant gliomas, powerfully demonstrating the existence of tumor suppressor genes in this region. Consistent with the previous studies, the most common deletion interval has been mapped to a roughly 4Mb region of 19q13.3 between the APOC2 and HRC genes, between genetic markers D19S219 and D19S246. EML2 is a tumor suppressor gene that is located on 19q13.32 and is considerably methylated in high-grade gliomas. Notably, MIR330 gene that is situated within the non-coding intronic region of EML2 is also detected as an oncosuppressor-miR in a variety of cancers including gliomas. Additionally, glioma oncoprotein Bcl2L12 which is located on 19q13.33 is significantly overexpressed in glioblastoma multiform and has a pivotal role in cancer evolution and resistance to apoptosis. Other genes such as MIR519D and NOP53 are also discovered as tumor suppressor genes in gliomas which are located on 19q13.3 and 19q13.4, respectively. Therefore, we hypothesize that a CRISPR/AsCpf1-based genome engineering strategy might be utilized to attach these deleted sizeable chromosomal portions of genes coding tumor suppressors as vital parts of the chromosome 19 q-arm with the purpose of treatment of this chromosomal abnormality in gliomas. Also, we can concurrently employ the CRISPR-ddAsCpf1 strategy for the precise suppression of Bcl2L12 oncogene in glioma.