Searching for the needle in the haystack: deconvoluting the evolutionary dynamics of residual disease in human glioblastoma

K Litchfield,S Turajlic,S.T.C Shepherd

doi:10.1093/annonc/mdz042

K Litchfield, S Turajlic + Show 1 more

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https://doi.org/10.1093/annonc/mdz042

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Abstract

Searching for the needle in the haystack: deconvoluting the evolutionary dynamics of residual disease in human glioblastoma

Highlights

The evolution of divergent subpopulations of cancer cells within the same tumour has been proposed to underlie the development of treatment resistance and the recurrence of malignancy across multiple tumour types [1]. In this issue of Annals of Oncology, Spiteri et al [2] utilise multi-region whole-exome sequencing to unravel the complex nature of cancer evolution in time and space that underlies glioblastoma (GBM) recurrence and offer novel insights into the phylogenetic relationships between the initial bulk tumour mass, clinically occult residual disease following initial radical therapy, and relapsed GBM
In the two cases where tissue was available at relapse, the 356 | Shepherd et al Editorials recurrent tumour bulk and GBM cells in the sub-ventricular zone (SVZ) had acquired several new mutations, but no de novo mutations were detected at the infiltrative margin at recurrence
The work from Spiteri et al corroborates the recent findings of Lee et al [14] who published data derived from 28 patients with GBM, suggesting that the human SVZ harbours cells containing low-frequency GBM driver mutations that migrate to other parts of the brain and give rise to malignant glioma

Summary

Introduction

Hotta K, Aoe K, Kozuki T et al A phase II study of trastuzumab emtansine in HER2-positive non-small cell lung cancer. In this issue of Annals of Oncology, Spiteri et al [2] utilise multi-region whole-exome sequencing to unravel the complex nature of cancer evolution in time and space that underlies glioblastoma (GBM) recurrence and offer novel insights into the phylogenetic relationships between the initial bulk tumour mass, clinically occult residual disease following initial radical therapy, and relapsed GBM.

Results

Conclusion