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Genetic and clinical characteristics of primary and secondary glioblastoma is associated with differential molecular subtype distribution.

Li R, Li H, Yan W, Yang P, Bao Z, Zhang C, Jiang T, You Y - Oncotarget (2015)

Bottom Line: Mutations in isocitrate dehydrogenase-1 (IDH1) were found to be highly concentrated in the Proneural subtypes.In addition, patients with sGBM were 10 years younger on average than those with pGBM, and exhibited clinical features of shorter overall survival and frontal lobe tumor location tendency.Overall, these results reveal the intrinsic distinction between pGBM and sGBM, and provide insight into the genetic and clinical attributes of GBM.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

ABSTRACT
Glioblastoma multiforme (GBM) is classified into primary (pGBM) or secondary (sGBM) based on clinical progression. However, there are some limits to this classification for insight into genetically and clinically distinction between pGBM and sGBM. The aim of this study is to characterize pGBM and sGBM associating with differential molecular subtype distribution. Whole transcriptome sequencing data was used to assess the distribution of molecular subtypes and genetic alterations in 88 pGBM and 34 sGBM in a Chinese population-based cohort, and the biological progression and prognostic impact were analyzed by combining clinical information. Forty-one percentage of pGBM were designated as Mesenchymal subtype, while only 15% were the Proneural subtype. However, sGBM displayed the opposite ratio of Mesenchymal (15%) and Proneural (44%) subtypes. Mutations in isocitrate dehydrogenase-1 (IDH1) were found to be highly concentrated in the Proneural subtypes. In addition, patients with sGBM were 10 years younger on average than those with pGBM, and exhibited clinical features of shorter overall survival and frontal lobe tumor location tendency. Furthermore, in sGBM, gene sets related to malignant progression were found to be enriched. Overall, these results reveal the intrinsic distinction between pGBM and sGBM, and provide insight into the genetic and clinical attributes of GBM.

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Age distribution of patients with GBM(A) Distribution of molecular subtypes in pGBM and sGBM; (B) Age distribution of patients with molecular and clinical subtypes of GBM; (C) Age distribution of patients with four molecular subtypes of GBM. *, P<0.05; **, P<0.01; ****, P<0.0001.
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Figure 4: Age distribution of patients with GBM(A) Distribution of molecular subtypes in pGBM and sGBM; (B) Age distribution of patients with molecular and clinical subtypes of GBM; (C) Age distribution of patients with four molecular subtypes of GBM. *, P<0.05; **, P<0.01; ****, P<0.0001.

Mentions: As shown in (Figure 4), GBM predominantly affected males in this study, with a male to female ratio of 1.67 in pGBM and 2.4 in sGBM. With respect to anatomical localization, the frontal and temporal lobe were the most commonly involved sites, with 68% of sGBM located in the frontal lobe, while only one case involved the temporal lobe. A similar phenomenon was observed in Proneural (45%), Classical (38%) and Neural (58%) subtypes. However, among Mesenchymal subtypes, the temporal lobe was found to be the predominant site (41%). pGBM show widespread anatomical distribution and tumors were more commonly located in the center hemisphere of the brain. The mean age of patients diagnosed with sGBM was 39.26 ± 2.05 years, whereas the mean age of patients diagnosed with pGBM was 49.61 ± 1.35 years. For the molecular subtypes, the cohort with the oldest age of diagnosis was Mesenchymal subtype (52.06 ± 1.64 years), followed by Neural (50.75 ± 3.07 years), Classical (45.50 ± 1.92 years) and Proneural (39.48 ± 1.65 years). The age distribution of the four molecular subtypes in pGBM and sGBM was further analyzed, and patients with Classical subtype sGBM were found to be significantly younger than those with same subtype in pGBM (mean age of 36.45 versus 47.97 years; P= 0.0125). This trend was also observed for Mesenchymal subtype (46.60 years for sGBM versus 53.89 for pGBM [P=0.2241]), and Neural subtype (41.00 years for sGBM versus 54.43 years for pGBM [P=0.0934]), whereas Proneural subtypes had similar age of diagnosis (38.53 years for sGBM versus 39.23 years for pGBM [P=0.8552]).


Genetic and clinical characteristics of primary and secondary glioblastoma is associated with differential molecular subtype distribution.

Li R, Li H, Yan W, Yang P, Bao Z, Zhang C, Jiang T, You Y - Oncotarget (2015)

Age distribution of patients with GBM(A) Distribution of molecular subtypes in pGBM and sGBM; (B) Age distribution of patients with molecular and clinical subtypes of GBM; (C) Age distribution of patients with four molecular subtypes of GBM. *, P<0.05; **, P<0.01; ****, P<0.0001.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4466687&req=5

Figure 4: Age distribution of patients with GBM(A) Distribution of molecular subtypes in pGBM and sGBM; (B) Age distribution of patients with molecular and clinical subtypes of GBM; (C) Age distribution of patients with four molecular subtypes of GBM. *, P<0.05; **, P<0.01; ****, P<0.0001.
Mentions: As shown in (Figure 4), GBM predominantly affected males in this study, with a male to female ratio of 1.67 in pGBM and 2.4 in sGBM. With respect to anatomical localization, the frontal and temporal lobe were the most commonly involved sites, with 68% of sGBM located in the frontal lobe, while only one case involved the temporal lobe. A similar phenomenon was observed in Proneural (45%), Classical (38%) and Neural (58%) subtypes. However, among Mesenchymal subtypes, the temporal lobe was found to be the predominant site (41%). pGBM show widespread anatomical distribution and tumors were more commonly located in the center hemisphere of the brain. The mean age of patients diagnosed with sGBM was 39.26 ± 2.05 years, whereas the mean age of patients diagnosed with pGBM was 49.61 ± 1.35 years. For the molecular subtypes, the cohort with the oldest age of diagnosis was Mesenchymal subtype (52.06 ± 1.64 years), followed by Neural (50.75 ± 3.07 years), Classical (45.50 ± 1.92 years) and Proneural (39.48 ± 1.65 years). The age distribution of the four molecular subtypes in pGBM and sGBM was further analyzed, and patients with Classical subtype sGBM were found to be significantly younger than those with same subtype in pGBM (mean age of 36.45 versus 47.97 years; P= 0.0125). This trend was also observed for Mesenchymal subtype (46.60 years for sGBM versus 53.89 for pGBM [P=0.2241]), and Neural subtype (41.00 years for sGBM versus 54.43 years for pGBM [P=0.0934]), whereas Proneural subtypes had similar age of diagnosis (38.53 years for sGBM versus 39.23 years for pGBM [P=0.8552]).

Bottom Line: Mutations in isocitrate dehydrogenase-1 (IDH1) were found to be highly concentrated in the Proneural subtypes.In addition, patients with sGBM were 10 years younger on average than those with pGBM, and exhibited clinical features of shorter overall survival and frontal lobe tumor location tendency.Overall, these results reveal the intrinsic distinction between pGBM and sGBM, and provide insight into the genetic and clinical attributes of GBM.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

ABSTRACT
Glioblastoma multiforme (GBM) is classified into primary (pGBM) or secondary (sGBM) based on clinical progression. However, there are some limits to this classification for insight into genetically and clinically distinction between pGBM and sGBM. The aim of this study is to characterize pGBM and sGBM associating with differential molecular subtype distribution. Whole transcriptome sequencing data was used to assess the distribution of molecular subtypes and genetic alterations in 88 pGBM and 34 sGBM in a Chinese population-based cohort, and the biological progression and prognostic impact were analyzed by combining clinical information. Forty-one percentage of pGBM were designated as Mesenchymal subtype, while only 15% were the Proneural subtype. However, sGBM displayed the opposite ratio of Mesenchymal (15%) and Proneural (44%) subtypes. Mutations in isocitrate dehydrogenase-1 (IDH1) were found to be highly concentrated in the Proneural subtypes. In addition, patients with sGBM were 10 years younger on average than those with pGBM, and exhibited clinical features of shorter overall survival and frontal lobe tumor location tendency. Furthermore, in sGBM, gene sets related to malignant progression were found to be enriched. Overall, these results reveal the intrinsic distinction between pGBM and sGBM, and provide insight into the genetic and clinical attributes of GBM.

Show MeSH
Related in: MedlinePlus