1p36 is a preferential target of chromosome 1 deletions in astrocytic tumours and homozygously deleted in a subset of glioblastomas

Abstract

Astrocytic, oligodendroglial and mixed gliomas are the commonest gliomas in adults. They have distinct phenotypes and clinical courses, but as they exist as a continuous histological spectrum, differentiating them can be difficult. Co-deletions of total 1p and 19q are found in the majority of oligodendrogliomas and considered as a diagnostic marker and a prognostic indicator. The 1p status of astrocytomas has not yet been thoroughly examined. Using a chromosome 1 tile path array, we investigated 108 adult astrocytic tumours for copy number alterations. Total 1p deletions were rare (2%), however partial deletions involving 1p36 were frequently identified in anaplastic astrocytomas (22%) and glioblastomas (34%). Multivariate analysis showed that patients with total 1p deletions had significantly longer survival (P ¼ 0.005). In nine glioblastomas homozygous deletions at 1p36 were identified. No somatic mutations were found among the five genes located in the homozygously deleted region. However, the CpG island of TNFRSF9 was hypermethylated in 19% of astrocytic tumours and 87% of glioma cell lines. TNFRSF9 expression was upregulated after demethylation of glioma cell lines. Akt3 amplifications were found in four glioblastomas. Our results indicate that 1p deletions are common anaplastic astrocytomas and glioblastomas but are distinct from the 1p abnormalities in oligodendrogliomas.

1p19q LOH patterns and expression of p53 and Olig2 in gliomas: relation with histological types and prognosis

“…In this study, oligodendrogliomas presented only two haplotypes, mainly whole loss and, in a minority of cases, arm retention, whereas the other patterns were found in glioblastoma multiforme. Other studies have reported that whole 1p loss is rare in astrocytomas and, conversely, that partial loss restricted to the 1p36 region is more frequent in anaplastic astrocytomas (22%), glioblastomas (34%) 8 and oligoastrocytomas (60%). 12 We found 1p telomeric loss limited to the 1p36 region in 25% of the astrocytomas and 35% of the oligoastrocytomas.…”

“…Complete 1p19q loss is associated with the classical oligodendroglial phenotype and has been shown to be correlated with significantly longer overall and progression-free survival, whereas partial 1p telomeric loss is mostly found in astrocytic tumors and is associated with a poor prognosis. 8,20 Thus, in practice, analyses of 1p and 19q loss analyses should distinguish between cases of whole loss and telomeric loss, based on the use of appropriate FISH probes, comparative genomic hybridization or microsatellite marker amplification by PCR, exploring the entire chromosomal arms.…”

“…2,13 1p36 (B7 Mb) and 19q13.3 (B0.9 Mb) have been identified as minimal regions of loss, 11,12,14,15 but 1p and 19q deletions involving the entire 1p and 19q arms have been described. 8,[16][17][18][19][20][21][22] As reported by some researchers, 23,24 the morphological characteristics of gliomas may be a source of variability concerning 1p and 19q loss. There is now a consensus that tumors with a typical clear cell component should be classified as classical oligodendrogliomas.…”

“…4,8 However, the frequency and type of 1p19q genomic alteration have been shown to be highly variable. 1p19q loss is reported in approximately 40-70% of classical forms of oligodendrogliomas [9][10][11][12] and in approximately 50% of oligoastrocytomas.…”

Genetic Profiling: Searching for Novel Genetic Aberrations in Glioblastoma

“…RTK-independent activation of this pathway in glioblastoma can occur via mutation or amplification of PIK3CA (p110a) [46,47], and PIK3CD (p110d) is also overexpressed in some gliomas [48]. Other amplified regions containing oncogenes, for example AKT3 [22,49] and CCND2 [22,27].…”