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Reconstructing the molecular life history of gliomas.

ABSTRACT: At the time of their clinical manifestation, the heterogeneous group of adult and pediatric gliomas carries a wide range of diverse somatic genomic alterations, ranging from somatic single-nucleotide variants to structural chromosomal rearrangements. Somatic abnormalities may have functional consequences, such as a decrease, increase or change in mRNA transcripts, and cells pay a penalty for maintaining them. These abnormalities, therefore, must provide cells with a competitive advantage to become engrained into the glioma genome. Here, we propose a model of gliomagenesis consisting of the following five consecutive phases that glioma cells have traversed prior to clinical manifestation: (I) initial growth; (II) oncogene-induced senescence; (III) stressed growth; (IV) replicative senescence/crisis; (V) immortal growth. We have integrated the findings from a large number of studies in biology and (neuro)oncology and relate somatic alterations and other results discussed in these papers to each of these five phases. Understanding the story that each glioma tells at presentation may ultimately facilitate the design of novel, more effective therapeutic approaches.

SUBMITTER: Barthel FP

PROVIDER: S-EPMC5904231 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Reconstructing the molecular life history of gliomas.

Barthel Floris P FP Wesseling Pieter P Verhaak Roel G W RGW

Acta neuropathologica 20180403 5

At the time of their clinical manifestation, the heterogeneous group of adult and pediatric gliomas carries a wide range of diverse somatic genomic alterations, ranging from somatic single-nucleotide variants to structural chromosomal rearrangements. Somatic abnormalities may have functional consequences, such as a decrease, increase or change in mRNA transcripts, and cells pay a penalty for maintaining them. These abnormalities, therefore, must provide cells with a competitive advantage to beco ...[more]

PMID: 29616301

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Project description:Factors influencing the hominoid life histories are poorly understood, and little is known about how ecological conditions modulate the pace of their development. Yet our limited understanding of these interactions underpins life history interpretations in extinct hominins. Here we determined the synchronisation of dental mineralization/eruption with brain size in a 20th century museum collection of sympatric Gorilla gorilla and Pan troglodytes from Central Cameroon. Using δ13C and δ15N of individuals' hair, we assessed whether and how differences in diet and habitat use may have impacted on ape development. The results show that, overall, gorilla hair δ13C and δ15N values are more variable than those of chimpanzees, and that gorillas are consistently lower in δ13C and δ15N compared to chimpanzees. Within a restricted, isotopically-constrained area, gorilla brain development appears delayed relative to dental mineralization/eruption [or dental development is accelerated relative to brains]: only about 87.8% of adult brain size is attained by the time first permanent molars come into occlusion, whereas it is 92.3% in chimpanzees. Even when M1s are already in full functional occlusion, gorilla brains lag behind those of chimpanzee (91% versus 96.4%), relative to tooth development. Both bootstrap analyses and stable isotope results confirm that these results are unlikely due to sampling error. Rather, δ15N values imply that gorillas are not fully weaned (physiologically mature) until well after M1 are in full functional occlusion. In chimpanzees the transition from infant to adult feeding appears (a) more gradual and (b) earlier relative to somatic development. Taken together, the findings are consistent with life history theory that predicts delayed development when non-density dependent mortality is low, i.e. in closed habitats, and with the "risk aversion" hypothesis for frugivorous species as a means to avert starvation. Furthermore, the results highlight the complexity and plasticity of hominoid/hominin development.

Dataset Information

Reconstructing the molecular life history of gliomas.

Publications

Reconstructing the molecular life history of gliomas.

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