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A cancer tissue-specific FAM72 expression profile defines a novel glioblastoma multiform (GBM) gene-mutation signature

Title
A cancer tissue-specific FAM72 expression profile defines a novel glioblastoma multiform (GBM) gene-mutation signature
Author
Heese, Klaus
Keywords
Cancer; Glia; Glioblastoma; Neuron; SRGAP2; Stem cells; TCGA
Issue Date
2019-01
Publisher
SPRINGER
Citation
JOURNAL OF NEURO-ONCOLOGY, v.141, Issue1, Page. 57-70
Abstract
Introduction Glioblastoma multiform (GBM) is a neural stem cell (NSC)-derived malignant brain tumor with complex genetic alterations challenging clinical treatments. FAM72 is a NSC-specific protein comprised of four paralogous genes (FAM72 A-D) in the human genome, but its functional tumorigenic significance is unclear. Methods We conducted an in-depth expression and somatic mutation data analysis of FAM72 (A-D) in GBM using the comprehensive human clinical cancer study database cBioPortal [including The Cancer Genome Atlas (TCGA)]. Results We established a FAM72 transcription profile across 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. 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. Conclusion Our 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://link.springer.com/article/10.1007%2Fs11060-018-03029-3http://repository.hanyang.ac.kr/handle/20.500.11754/102781
ISSN
0167-594X; 1573-7373
DOI
10.1007/s11060-018-03029-3
Appears in Collections:
GRADUATE SCHOOL OF BIOMEDICAL SCIENCE AND ENGINEERING[S](의생명공학전문대학원) > ETC
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