| Id |
Subject |
Object |
Predicate |
Lexical cue |
| TextSentencer_T1 |
0-122 |
Sentence |
denotes |
Glioblastoma adaptation traced through decline of an IDH1 clonal driver and macro-evolution of a double-minute chromosome. |
| TextSentencer_T2 |
123-134 |
Sentence |
denotes |
BACKGROUND: |
| TextSentencer_T3 |
135-283 |
Sentence |
denotes |
Glioblastoma (GBM) is the most common malignant brain cancer occurring in adults, and is associated with dismal outcome and few therapeutic options. |
| TextSentencer_T4 |
284-430 |
Sentence |
denotes |
GBM has been shown to predominantly disrupt three core pathways through somatic aberrations, rendering it ideal for precision medicine approaches. |
| TextSentencer_T5 |
431-439 |
Sentence |
denotes |
METHODS: |
| TextSentencer_T6 |
440-620 |
Sentence |
denotes |
We describe a 35-year-old female patient with recurrent GBM following surgical removal of the primary tumour, adjuvant treatment with temozolomide and a 3-year disease-free period. |
| TextSentencer_T7 |
621-789 |
Sentence |
denotes |
Rapid whole-genome sequencing (WGS) of three separate tumour regions at recurrence was carried out and interpreted relative to WGS of two regions of the primary tumour. |
| TextSentencer_T8 |
790-798 |
Sentence |
denotes |
RESULTS: |
| TextSentencer_T9 |
799-885 |
Sentence |
denotes |
We found extensive mutational and copy-number heterogeneity within the primary tumour. |
| TextSentencer_T10 |
886-1001 |
Sentence |
denotes |
We identified a TP53 mutation and two focal amplifications involving PDGFRA, KIT and CDK4, on chromosomes 4 and 12. |
| TextSentencer_T11 |
1002-1139 |
Sentence |
denotes |
A clonal IDH1 R132H mutation in the primary, a known GBM driver event, was detectable at only very low frequency in the recurrent tumour. |
| TextSentencer_T12 |
1140-1372 |
Sentence |
denotes |
After sub-clonal diversification, evidence was found for a whole-genome doubling event and a translocation between the amplified regions of PDGFRA, KIT and CDK4, encoded within a double-minute chromosome also incorporating miR26a-2. |
| TextSentencer_T13 |
1373-1639 |
Sentence |
denotes |
The WGS analysis uncovered progressive evolution of the double-minute chromosome converging on the KIT/PDGFRA/PI3K/mTOR axis, superseding the IDH1 mutation in dominance in a mutually exclusive manner at recurrence, consequently the patient was treated with imatinib. |
| TextSentencer_T14 |
1640-1786 |
Sentence |
denotes |
Despite rapid sequencing and cancer genome-guided therapy against amplified oncogenes, the disease progressed, and the patient died shortly after. |
| TextSentencer_T15 |
1787-1798 |
Sentence |
denotes |
CONCLUSION: |
| TextSentencer_T16 |
1799-2016 |
Sentence |
denotes |
This case sheds light on the dynamic evolution of a GBM tumour, defining the origins of the lethal sub-clone, the macro-evolutionary genomic events dominating the disease at recurrence and the loss of a clonal driver. |
| TextSentencer_T17 |
2017-2141 |
Sentence |
denotes |
Even in the era of rapid WGS analysis, cases such as this illustrate the significant hurdles for precision medicine success. |
| T1 |
0-122 |
Sentence |
denotes |
Glioblastoma adaptation traced through decline of an IDH1 clonal driver and macro-evolution of a double-minute chromosome. |
| T2 |
123-134 |
Sentence |
denotes |
BACKGROUND: |
| T3 |
135-283 |
Sentence |
denotes |
Glioblastoma (GBM) is the most common malignant brain cancer occurring in adults, and is associated with dismal outcome and few therapeutic options. |
| T4 |
284-430 |
Sentence |
denotes |
GBM has been shown to predominantly disrupt three core pathways through somatic aberrations, rendering it ideal for precision medicine approaches. |
| T5 |
431-439 |
Sentence |
denotes |
METHODS: |
| T6 |
440-620 |
Sentence |
denotes |
We describe a 35-year-old female patient with recurrent GBM following surgical removal of the primary tumour, adjuvant treatment with temozolomide and a 3-year disease-free period. |
| T7 |
621-789 |
Sentence |
denotes |
Rapid whole-genome sequencing (WGS) of three separate tumour regions at recurrence was carried out and interpreted relative to WGS of two regions of the primary tumour. |
| T8 |
790-798 |
Sentence |
denotes |
RESULTS: |
| T9 |
799-885 |
Sentence |
denotes |
We found extensive mutational and copy-number heterogeneity within the primary tumour. |
| T10 |
886-1001 |
Sentence |
denotes |
We identified a TP53 mutation and two focal amplifications involving PDGFRA, KIT and CDK4, on chromosomes 4 and 12. |
| T11 |
1002-1139 |
Sentence |
denotes |
A clonal IDH1 R132H mutation in the primary, a known GBM driver event, was detectable at only very low frequency in the recurrent tumour. |
| T12 |
1140-1372 |
Sentence |
denotes |
After sub-clonal diversification, evidence was found for a whole-genome doubling event and a translocation between the amplified regions of PDGFRA, KIT and CDK4, encoded within a double-minute chromosome also incorporating miR26a-2. |
| T13 |
1373-1639 |
Sentence |
denotes |
The WGS analysis uncovered progressive evolution of the double-minute chromosome converging on the KIT/PDGFRA/PI3K/mTOR axis, superseding the IDH1 mutation in dominance in a mutually exclusive manner at recurrence, consequently the patient was treated with imatinib. |
| T14 |
1640-1786 |
Sentence |
denotes |
Despite rapid sequencing and cancer genome-guided therapy against amplified oncogenes, the disease progressed, and the patient died shortly after. |
| T15 |
1787-1798 |
Sentence |
denotes |
CONCLUSION: |
| T16 |
1799-2016 |
Sentence |
denotes |
This case sheds light on the dynamic evolution of a GBM tumour, defining the origins of the lethal sub-clone, the macro-evolutionary genomic events dominating the disease at recurrence and the loss of a clonal driver. |
| T17 |
2017-2141 |
Sentence |
denotes |
Even in the era of rapid WGS analysis, cases such as this illustrate the significant hurdles for precision medicine success. |
