Intratumoral patterns of clonal evolution in gliomas

Abstract

Few studies have explored the patterns of clonal evolution in gliomas. Here, we investigate the cytogenetic patterns of intratumoral clonal evolution of gliomas and their impact on tumor histopathology and patient survival. Cytogenetic analysis of 90 gliomas was performed in individual tumor cells (>200 cells/tumor) using multicolor (N=16 probes) interphase-FISH. Overall, chromosome gains were more frequent than chromosome losses. Gains of chromosome 7 and/or EGFR amplification were detected in 91% of the cases, whereas del(9p21) (77%) and del(10q23) (78%) were the most frequent chromosome losses. Virtually, all cases (99%) showed ≥2 tumor cell clones, with higher numbers among high-versus low-grade gliomas (p=0.001). Nine different cytogenetic patterns were found in the ancestral tumor clones.In most gliomas, ancestral clones showed abnormalities of chromosome 7, 9p, and/or 10q and cytogenetic evolution consisted of acquisition of additional abnormalities followed by tetraploidization. Conversely, early tetraploidization was associated with low-grade astrocytomas-2/3 pilocytic and 3/ 6 grade II diffuse astrocytomas-and combined loss of 1p36/ 19q13 with oligodendrogliomas, respectively; both aberrations were associated with a better patient outcome (p=0.03). Overall, our results support the existence of different pathways of intratumoral evolution in gliomas

Fluorescence in situ hybridization (FISH): an increasingly demanded tool for biomarker research and personalized medicine

“…LAVysion FISH, a four-color FISH kit for simultaneously detecting chromosome 6 and the 5p15, 7p12 (EGFR gene), and 8q24 (MYC gene) loci was developed to assist in the differential diagnosis of ambiguous lung cancers [87]. In recent years, qmFISH has been used in genetic variegation and clonal evolution studies of both hematological and non-hematological cancers [88-92]. …”

Detailed Characterization of Alterations of Chromosomes 7, 9, and 10 in Glioblastomas as Assessed by Single-Nucleotide Polymorphism Arrays

“…In line with this hypothesis, we have recently shown the existence of distinct cytogenetic pathways in gliomas, by using interphase fluorescence in situ hybridization (iFISH) analysis of intratumoral patterns of chromosomal alterations, at the single-cell level. 16 Notably, specific genomic aberrations and cytogenetic profiles are associated with particular tumor histo-pathologic features. [17][18][19] Accordingly, amplification (or rearrangement) of EGFR is almost restricted to a fraction of all malignant gliomas, particularly glioblastomas.…”

Somatic neurofibromatosis type 1 (NF1) inactivation characterizes NF1-associated pilocytic astrocytoma

“…Second, we demonstrate that NF1-PA have a monoclonal origin, similar to their sporadic counterparts (Payton et al 2011). While the majority of studies that examined clonal origins of glioma using single X-chromosome loci, fluorescent in situ hybridization, microsatellite markers, or single substitute mutation methods demonstrated a monoclonal pattern (Kattar et al 1997;Zhu et al 1997;Mueller et al 2001), there are reports of gliomas exhibiting a multiclonal origin (Dong et al 2002;Gomori et al 2002;Vital et al 2010). Since the few brain tumors with presumed polyclonal origins were high-grade gliomas, we favor a model of low-grade pediatric astrocytoma development in which tumors arise from a single population of glial progenitors during fetal or early postnatal life.…”