A cancer tissue-specific FAM72 expression profile defines a novel glioblastoma multiform (GBM) gene-mutation signature
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.
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)].
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.
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.
KeywordsCancer Glia Glioblastoma Neuron SRGAP2 Stem cells TCGA
This study was supported by Hanyang University by providing a scholarship to C.S.R. and by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2015R1D1A1A01057243 and 2016R1D1A1B03932599).
Compliance with ethical standards
Conflict of interest
The authors declare no conflicts of interest.
This article does not contain any studies with human participants or animals performed by any of the authors.
- 12.Rajan P, Stockley J, Sudbery IM et al (2014) Identification of a candidate prognostic gene signature by transcriptome analysis of matched pre- and post-treatment prostatic biopsies from patients with advanced prostate cancer. BMC Cancer 14:977. https://doi.org/10.1186/1471-2407-14-977 CrossRefGoogle Scholar
- 16.Team BD (2014) Bokeh: python library for interactive visualization. http://www.bokeh.pydata.org
- 28.Cloughesy TF, Cavenee WK, Mischel PS (2014) Glioblastoma: from molecular pathology to targeted treatment. Annu Rev Pathol 9:1–25. https://doi.org/10.1146/annurev-pathol-011110-130324 CrossRefGoogle Scholar
- 40.Zhao M, Jia W, Jiang WG et al (2016) ADAM29 expression in human breast cancer and its effects on breast cancer cells in vitro. Anticancer Res 36:1251–1258Google Scholar