Genetic secrets of long-term glioblastoma survivors.

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Abstract

Glioblastomas account for the majority of primary brain tumors. Although glioblastomas are considered as rare diseases, they represent 60%-70% of all gliomas and in most cases have fatal consequences. Genetic analyses show great heterogeneity both intratumor and intertumor. This notion opens up debates about glioblastoma origin. Different brain cells including astrocytes, neural stem cells, oligodendrocyte precursor cells and glioblastoma stem cells are proposed as capable of initiation and reseeding a tumor; however data is still inconclusive. Due to high mortality rate, long term glioblastoma survivors are defined as patients who live longer than 2 years post diagnosis. Extreme survivors, living 10 years or more after diagnosis, comprise less than 1% of all patients. Molecular testing suggests differences in the genetic profiles of glioblastoma between short and long term survivors. The most informative indicators are IDH mutations and MGMT promotor methylation. Other genes like FBLN4, EMP3, IGFBP-2, IGFBP-3, LGALS3, MAOB, PDPN, SERPING1 and TIMP1 have also been associated with glioblastoma prolonged survival. Emerging evidence proposes roles of different microRNAs in predicting patient survival. Moreover, clinical features like seizures as a symptom at presentation, age at diagnosis, and the extent of the surgical resection are also factors that influence the length of survival. Because of the small number of long term survivors, it is difficult to examine these samples and draw conclusions about the genetics of glioblastoma longevity. To aid in the clinical care, a thorough "omics" approach is necessary for identifying differences between short and long term glioblastoma survivors.