The evolutionary pattern of mutations in glioblastoma reveals therapy-mediated selection

Oncotarget
Andrea M MuscatDavid M Ashley

Abstract

Glioblastoma presents as a heterogeneous disease with poor prognosis despite the use of multimodal therapy. Analysis of genomic DNA changes between initial diagnosis and recurrence in response to standard treatment protocols would enhance understanding of disease progression and better inform new treatment strategies. A cohort of 21 patients with primary glioblastoma were examined between diagnosis and first recurrence. This study presented a rare opportunity to characterize molecular alterations in tumors observed in three patients who received no therapeutic intervention, other than surgery, offering a unique control. We focused this study by comparing the dynamic mutation profiles between the primary tumors and their matched recurrent counterparts. Molecular profiling of tumors was performed using multiplexed targeted deep sequencing of 409 well characterized cancer-associated genes, achieving a mean read depth of 1272 x. Three levels of evidence suggested an evolutionary pattern consistent with a response to therapy-mediated selection pressures exists in treated patients: 1) variant burden was reduced in recurrent tumors, 2) neutral evolutionary dynamics apparent in untreated tumors shifted toward a non-neutral mode of evol...Continue Reading

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Citations

Apr 19, 2018·Critical Reviews in Clinical Laboratory Sciences·Ivana Jovčevska
Aug 4, 2019·Pathology Oncology Research : POR·Zoltan Kraboth, Bernadette Kalman
Dec 12, 2018·Journal of Neuro-oncology·Beth K NeilsenMichele R Aizenberg
Aug 9, 2020·Frontiers in Immunology·Syreeta DeCordovaUday Kishore
Aug 12, 2020·Journal of Cancer Research and Clinical Oncology·Zoltan KrabothBernadette Kalman
Dec 7, 2019·Nature Reviews. Cancer·John H SampsonDavid M Ashley
Jan 27, 2021·Current Oncology Reports·Abigail L MendeJennifer L Clarke
Dec 31, 2020·Cancers·Cristina BirzuGiuseppe Lombardi
Mar 7, 2021·Cancers·Hong-My NguyenDipongkor Saha
Apr 4, 2021·Genes·Parvaneh MahinfarBehzad Mansoori
Jul 3, 2021·Tomography : a Journal for Imaging Research·Taejin L MinBrent D Weinberg

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Datasets Mentioned

BETA
SRP080827

Methods Mentioned

BETA
surgical resection
Assay
chip

Software Mentioned

OncoPrint
COSMIC
Ion [UNK]
Protein Variation Effect Analyzer ( PROVEAN )
MuTect
Minitab ®
- Proton - Low Stringency Variant Caller Plugin
ABSOLUTE
SIFT
Ion Torrent Software Suite

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