Abstract：
PURPOSE:Glioblastoma (GBM) is characterized by extensive clonal diversity suggesting the presence of tumor cells with varying degrees of treatment sensitivity. Radiotherapy is an integral part of glioblastoma treatment. Whether GBMs are comprised of spatially distinct cellular populations with uniform or varying degrees of radiosensitivity has not been established. METHODS:Spatially distinct regions of three GBMs (J3, J7 and J14) were resected and unique cell lines were derived from each region. DNA from cell lines, corresponding tumor fragments, and patient blood was extracted for whole exome sequencing. Variants, clonal composition, and functional implications were compared and analyzed with superFreq and IPA. Limiting dilution assays were performed on cell lines to measure intrinsic radiosensitivity. RESULTS:Based on WES, cell lines generated from different regions of the same tumor were more closely correlated with their tumor of origin than the other GBMs. Variant and clonal composition comparisons showed that cell lines from distinct tumors displayed increasing levels of ITH with J3 and J14 having the lowest and highest, respectively. The radiosensitivities of the cell lines generated from the J3 tumor were similar as were those generated from the J7 tumor. However, the radiosensitivities of the 2 cell lines generated from the J14 tumor (J14T3 and J14T6) were significantly different with J14T6 being more sensitive than J14T3. CONCLUSION:Data suggest a tumor dependent ITH in radiosensitivity. The existence of ITH in radiosensitivity may impact not only the initial therapeutic response but also the effectiveness of retreatment protocols.
journal_name
J Neurooncoljournal_title
Journal of neuro-oncologyauthors
McAbee JH,Degorre-Kerbaul C,Valdez K,Wendler A,Shankavaram UT,Watts C,Camphausen K,Tofilon PJdoi
10.1007/s11060-020-03643-0subject
Has Abstractpub_date
2020-09-01 00:00:00pages
383-390issue
3eissn
0167-594Xissn
1573-7373pii
10.1007/s11060-020-03643-0journal_volume
149pub_type
杂志文章abstract：:Previous studies have shown an inverse association between allergies and glioma risk; however, results for associations between single nucleotide polymorphisms (SNPs) of allergy-related genes and glioma risk have been inconsistent and restricted to a small number of SNPs. The objective of this study was to examine the...
journal_title：Journal of neuro-oncology
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journal_title：Journal of neuro-oncology
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journal_title：Journal of neuro-oncology
pub_type： 杂志文章,随机对照试验
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journal_title：Journal of neuro-oncology
pub_type： 杂志文章
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更新日期：1996-01-01 00:00:00
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pub_type： 杂志文章,评审
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更新日期：2020-11-01 00:00:00
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journal_title：Journal of neuro-oncology
pub_type： 杂志文章
doi：10.1007/s11060-011-0647-9
更新日期：2012-01-01 00:00:00
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journal_title：Journal of neuro-oncology
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doi：10.1023/a:1005761031077
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