TY - JOUR
T1 - Reconstructing the molecular life history of gliomas
AU - Barthel, Floris P.
AU - Wesseling, Pieter
AU - Verhaak, Roel G. W.
PY - 2018
Y1 - 2018
N2 - 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.
AB - 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.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85044759427&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/29616301
U2 - https://doi.org/10.1007/s00401-018-1842-y
DO - https://doi.org/10.1007/s00401-018-1842-y
M3 - Review article
C2 - 29616301
SN - 0001-6322
VL - 135
SP - 649
EP - 670
JO - Acta neuropathologica
JF - Acta neuropathologica
IS - 5
ER -