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FAM72 – a control switch for cancer? A cancer tissue-specific FAM72 expression signature analysis

Title
FAM72 – a control switch for cancer? A cancer tissue-specific FAM72 expression signature analysis
Author
Chinmay Satish Rahane
Alternative Author(s)
친매이사티쉬라한
Advisor(s)
Klaus Heese
Issue Date
2019-02
Publisher
한양대학교
Degree
Doctor
Abstract
FAM72 is a neural stem cell (NSC)-specific protein comprised of four paralogous genes (FAM72 A-D) in the human genome, but its functional tumorigenic significance is unclear. I conducted an in-depth in silico mRNA expression and somatic mutation data analysis of FAM72 (A-D), using the comprehensive public cBioPortal human cancer study database, to decipher the functional tumorigenic significance of neural FAM72 in non-neuronal tissue. I established a FAM72 transcription profile across The Cancer Genome Atlas (TCGA) correlated with the expression of the proliferative marker MKI67 and a tissue-specific gene-mutation signature represented by pivotal genes involved in driving the cell cycle. FAM72 paralogs are overexpressed in cancer cells, specifically correlating with the mitotic cell cycle genes ASPM, KIF14, KIF23, CENPE, CENPE, CEP55, SGO1, and BUB1, thereby contributing to centrosome and mitotic spindle formation. Common transcription factor binding sites (TFBS) in the regulatory region of the FAM72 gene, determined through the JASPAR eukaryotic TFBS and Ensembl databases, confirm co-expression and co-regulation of FAM72 with these M-phase cell cycle genes, thereby contributing to centrosome and mitotic spindle formation. As FAM72 is an NSC-specific protein, I focused on the oncogene mutation-FAM72 expression status in the brain cancer glioblastoma multiforme (GBM). FAM72 expression correlation identifies a novel GBM-specific gene set (SCN9A, MXRA5, ADAM29, KDR, LRP1B, and PIK3C2G) in the de novo pathway of primary GBM predestined as viable targets for therapeutics. My newly identified primary GBM-specific gene-mutation signature, along with FAM72, could thus provide a new basis for prognostic biomarkers for diagnostics of GBM and could serve as potential therapeutic targets.
URI
https://repository.hanyang.ac.kr/handle/20.500.11754/99941http://hanyang.dcollection.net/common/orgView/200000434526
Appears in Collections:
GRADUATE SCHOOL OF BIOMEDICAL SCIENCE AND ENGINEERING[S](의생명공학전문대학원) > BIOMEDICAL SCIENCE(의생명과학과) > Theses (Ph.D.)
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