TY  - JOUR
AU  - Zhang, Jinsen
AU  - Feng, Yuan
AU  - Li, Guanghao
AU  - Zhang, Jianhua
AU  - Zhang, Xin
AU  - Zhang, Yi
AU  - Qin, Zhiyong
AU  - Zhuang, Dongxiao
AU  - Qiu, Tianming
AU  - Shi, Zhifeng
AU  - Zhu, Wei
AU  - Zhang, Rui
AU  - Wu, Yonghe
AU  - Liu, Haikun
AU  - Cao, Dandan
AU  - Hua, Wei
AU  - Mao, Ying
TI  - Distinct aneuploid evolution of astrocytoma and glioblastoma during recurrence.
JO  - npj precision oncology
VL  - 7
IS  - 1
SN  - 2397-768X
CY  - [London]
PB  - Springer Nature
M1  - DKFZ-2023-01927
SP  - 97
PY  - 2023
N1  - DKFZ-ZMBH Alliance
AB  - Astrocytoma and glioblastoma (GB) are reclassified subtypes of adult diffuse gliomas based on distinct isocitrate dehydrogenase (IDH) mutation in the fifth edition of the WHO Classification of Tumors of the Central Nervous System. The recurrence of gliomas is a common and inevitable challenge, and analyzing the distinct genomic alterations in astrocytoma and GB could provide insights into their progression. This study conducted a longitudinal investigation, utilizing whole-exome sequencing, on 65 paired primary/recurrent gliomas. It examined chromosome arm aneuploidies, copy number variations (CNVs) of cancer-related genes and pathway enrichments during the relapse. The veracity of these findings was verified through the integration of our data with multiple public resources and by corroborative immunohistochemistry (IHC). The results revealed a greater prevalence of aneuploidy changes and acquired CNVs in recurrent lower grade astrocytoma than in relapsed grade 4 astrocytoma and GB. Larger aneuploidy changes were predictive of an unfavorable prognosis in lower grade astrocytoma (P < 0.05). Further, patients with acquired gains of 1q, 6p or loss of 13q at recurrence had a shorter overall survival in lower grade astrocytoma (P < 0.05); however, these prognostic effects were confined in grade 4 astrocytoma and GB. Moreover, acquired gains of 12 genes (including VEGFA) on 6p during relapse were associated with unfavorable prognosis for lower grade astrocytoma patients. Notably, elevated VEGFA expression during recurrence corresponded to poorer survival, validated through IHC and CGGA data. To summarize, these findings offer valuable insights into the progression of gliomas and have implications for guiding therapeutic approaches during recurrence.
LB  - PUB:(DE-HGF)16
C6  - pmid:37741941
C2  - pmc:PMC10517995
DO  - DOI:10.1038/s41698-023-00453-1
UR  - https://inrepo02.dkfz.de/record/283140
ER  -