Frequency and clinical significance of chromosome 7 and 10 aneuploidies, amplification of the EGFR gene, deletion of PTEN and TP53 genes, and 1p/19q deficiency in a sample of adult patients diagnosed with glioblastoma from Southern Brazil

Abstract

Glioblastoma stands out as the most frequent central nervous system neoplasia, presenting a poor prognosis. The aim of this study was to verify the frequency and clinical significance of the aneuploidy of chromosomes 7 and 10, EGFR amplification, PTEN and TP53 deletions and 1p/19q deficiency in adult patients diagnosed with glioblastoma. The sample consisted of 40 patients treated from November 2011 to March 2015 at two major neurosurgery services from Southern Brazil. Molecular cytogenetic analyses of the tumor were performed through fluorescent in situ hybridization (FISH). The clinical features evaluated consisted of age, sex, tumor location, clinical symptoms, family history of cancer, type of resection and survival. The mean age of the patients was 59.3 years (ranged from 41 to 83). Most of them were males (70%). The median survival was 145 days. Chromosome 10 monosomy was detected in 52.5% of the patients, chromosome 7 polysomy in 50%, EGFR amplification in 42.5%, PTEN deletion in 35%, TP53 deletion in 22.5%, 1p deletion in 5% and 19q deletion in 7.5%. Age was shown to be a prognostic factor, and patients with lower age presented higher survival (p = 0.042). TP53 and PTEN deletions had a negative impact on survival (p = 0.011 and p = 0.037, respectively). Our data suggest that TP53 and PTEN deletions may be associated with a poorer prognosis. These findings may have importance over prognosis determination and choice of the therapy to be administered.

Financially effective test algorithm to identify an aggressive, EGFR-amplified variant of IDH-wildtype, lower-grade diffuse glioma

“…Our proposed algorithm is readily scalable to enable meaningful genomic characterization of gliomas. [44][45][46][47] Therapeutically, EGFR signaling and downstream activation of receptor tyrosine kinase/Ras/phosphatidylinositol-3 kinase pathways have received significant attention in multiple cancer types. [48][49][50] Despite the relative success in lung and breast cancer, EGFR tyrosine kinase inhibitors have not shown significant response rates in gliomas to date, 51,52 and antibody-based therapies have been similarly disappointing.…”

Identification and validation of a three-gene signature as a candidate prognostic biomarker for lower grade glioma

“…So many central nervous system tumors were named according to molecular parameters and histopathologic diagnosis, especially gliomas, ependymomas and medulloblastomas in the 2016 revision of the WHO classification (Zhang et al, 2019b). As we know, some molecular markers, such as MGMT (O6-methylguanine DNA methyltransferase) (Binabaj et al, 2018), isocitrate dehydrogenase (IDH) (Kwon et al, 2019), epidermal growth factor receptor (EGFR) (Chistiakov, Chekhonin & Chekhonin, 2017) and phosphatase and tensin homolog (PTEN) (Koshiyama et al, 2017) that have contributed to personalized therapeutic approaches and targeted anti-glioblastoma therapies have been routinely tested in glioblastoma patients clinically (Yin et al, 2019). However, there are few specific clinical indicators and therapeutic targets for LGGs compared to glioblastoma, so there is an urgent need to elucidate the mechanism of glioma development and progression, which can provide potential treatment targets for LGGs.…”

Peer Review #1 of "Identification and validation of a three-gene signature as a candidate prognostic biomarker for lower grade glioma (v0.1)"

“…So many central nervous system tumors were named according to molecular parameters and histopathologic diagnosis， especially gliomas，ependymomas，and medulloblastomas in the 2016 revision of the WHO classification (Zhang et al 2019b). As we know，some molecular markers，such as MGMT(O6methylguanine DNA methyltransferase) (Binabaj et al 2018)，IDH(isocitrate dehydrogenase) (Kwon et al 2019)，EGFR(epidermal growth factor receptor) (Chistiakov et al 2017)，and PTEN(phosphatase and tensin homolog) (Koshiyama et al 2017)that have contributed to personalized therapeutic approaches and targeted anti-glioblastoma therapies have been routinely tested in glioblastoma patients clinically (Yin et al 2019). However there are few specific clinical indicators and therapeutic targets for LGGs compared to glioblastoma，so it is urgent to elucidate the mechanism of glioma development and progression，which can provide potential treatment targets for LGGs.…”