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SEL1L SNP rs12435998, a predictor of glioblastoma survival and response to radio-chemotherapy.

Mellai M, Cattaneo M, Storaci AM, Annovazzi L, Cassoni P, Melcarne A, De Blasio P, Schiffer D, Biunno I - Oncotarget (2015)

Bottom Line: The suppressor of Lin-12-like (C. elegans) (SEL1L) is involved in the endoplasmic reticulum (ER)-associated degradation pathway, malignant transformation and stem cells.In GBM patients, the SNP rs12435998 was associated with prolonged overall survival (OS) and better response to TMZ-based radio-chemotherapy.GBM stem cells with this SNP showed lower levels of SEL1L expression and enhanced sensitivity to VPA.

View Article: PubMed Central - PubMed

Affiliation: Neuro-Bio-Oncology Center/Policlinico di Monza Foundation, Vercelli 13100, Italy.

ABSTRACT
The suppressor of Lin-12-like (C. elegans) (SEL1L) is involved in the endoplasmic reticulum (ER)-associated degradation pathway, malignant transformation and stem cells. In 412 formalin-fixed and paraffin-embedded brain tumors and 39 Glioblastoma multiforme (GBM) cell lines, we determined the frequency of five SEL1L single nucleotide genetic variants with regulatory and coding functions by a SNaPShot™ assay. We tested their possible association with brain tumor risk, prognosis and therapy. We studied the in vitro cytotoxicity of valproic acid (VPA), temozolomide (TMZ), doxorubicin (DOX) and paclitaxel (PTX), alone or in combination, on 11 GBM cell lines, with respect to the SNP rs12435998 genotype. The SNP rs12435998 was prevalent in anaplastic and malignant gliomas, and in meningiomas of all histologic grades, but unrelated to brain tumor risks. In GBM patients, the SNP rs12435998 was associated with prolonged overall survival (OS) and better response to TMZ-based radio-chemotherapy. GBM stem cells with this SNP showed lower levels of SEL1L expression and enhanced sensitivity to VPA.

No MeSH data available.


Related in: MedlinePlus

SEL1L expression levels by qRT-PCR and analysis of SEL1L alternative transcripts in GBM cell linesA.SEL1L expression levels in NS and AC cultures with respect to the SEL1L SNP rs12435998 genotype. B. Analysis of SEL1L alternative transcripts in the same panel of GBM cell lines with respect to the SEL1L SNP rs12435998 genotype.Abbreviations: SEL1L, suppressor of lin-12-like; qRT-PCR, quantitative real time (qRT)-PCR; GBM, glioblastoma multiforme; SNP, single nucleotide polymorphism; NS, neurospheres; AC, adherent cells.
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Figure 2: SEL1L expression levels by qRT-PCR and analysis of SEL1L alternative transcripts in GBM cell linesA.SEL1L expression levels in NS and AC cultures with respect to the SEL1L SNP rs12435998 genotype. B. Analysis of SEL1L alternative transcripts in the same panel of GBM cell lines with respect to the SEL1L SNP rs12435998 genotype.Abbreviations: SEL1L, suppressor of lin-12-like; qRT-PCR, quantitative real time (qRT)-PCR; GBM, glioblastoma multiforme; SNP, single nucleotide polymorphism; NS, neurospheres; AC, adherent cells.

Mentions: SEL1L expression was evaluated in 18 GBM cell lines carrying different genotypes of the SNP rs12435998, in order to evaluate the influence on the mRNA. Five of these (CV1 NS, CV13 NS, CTO5 NS, NO6 NS and 010627 NS) were derived and grew as NS, six (CV2 AC, CV6 AC, CV9 AC, CV10 AC, CV17 AC and U87-MG AC) as AC, three (CV21, CTO3 and NO3) both as AC and NS, and one (G166) in coated matrix. Lower SEL1L mRNA expression levels were observed in NS compared to AC, and the minor allele C appeared to be associated in the former to lower SEL1L expression levels (Figure 2A). We also evaluated SOX2 and NOTCH1 gene expression and we found higher levels in NS compared to AC (Figure 3), with the exception of CTO3 cell line (carrying the CC genotype) where their expression was always high in both NS and AC. In contrast, the Gadd45β gene expression was higher in AC than in NS (Figure 3).


SEL1L SNP rs12435998, a predictor of glioblastoma survival and response to radio-chemotherapy.

Mellai M, Cattaneo M, Storaci AM, Annovazzi L, Cassoni P, Melcarne A, De Blasio P, Schiffer D, Biunno I - Oncotarget (2015)

SEL1L expression levels by qRT-PCR and analysis of SEL1L alternative transcripts in GBM cell linesA.SEL1L expression levels in NS and AC cultures with respect to the SEL1L SNP rs12435998 genotype. B. Analysis of SEL1L alternative transcripts in the same panel of GBM cell lines with respect to the SEL1L SNP rs12435998 genotype.Abbreviations: SEL1L, suppressor of lin-12-like; qRT-PCR, quantitative real time (qRT)-PCR; GBM, glioblastoma multiforme; SNP, single nucleotide polymorphism; NS, neurospheres; AC, adherent cells.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4494950&req=5

Figure 2: SEL1L expression levels by qRT-PCR and analysis of SEL1L alternative transcripts in GBM cell linesA.SEL1L expression levels in NS and AC cultures with respect to the SEL1L SNP rs12435998 genotype. B. Analysis of SEL1L alternative transcripts in the same panel of GBM cell lines with respect to the SEL1L SNP rs12435998 genotype.Abbreviations: SEL1L, suppressor of lin-12-like; qRT-PCR, quantitative real time (qRT)-PCR; GBM, glioblastoma multiforme; SNP, single nucleotide polymorphism; NS, neurospheres; AC, adherent cells.
Mentions: SEL1L expression was evaluated in 18 GBM cell lines carrying different genotypes of the SNP rs12435998, in order to evaluate the influence on the mRNA. Five of these (CV1 NS, CV13 NS, CTO5 NS, NO6 NS and 010627 NS) were derived and grew as NS, six (CV2 AC, CV6 AC, CV9 AC, CV10 AC, CV17 AC and U87-MG AC) as AC, three (CV21, CTO3 and NO3) both as AC and NS, and one (G166) in coated matrix. Lower SEL1L mRNA expression levels were observed in NS compared to AC, and the minor allele C appeared to be associated in the former to lower SEL1L expression levels (Figure 2A). We also evaluated SOX2 and NOTCH1 gene expression and we found higher levels in NS compared to AC (Figure 3), with the exception of CTO3 cell line (carrying the CC genotype) where their expression was always high in both NS and AC. In contrast, the Gadd45β gene expression was higher in AC than in NS (Figure 3).

Bottom Line: The suppressor of Lin-12-like (C. elegans) (SEL1L) is involved in the endoplasmic reticulum (ER)-associated degradation pathway, malignant transformation and stem cells.In GBM patients, the SNP rs12435998 was associated with prolonged overall survival (OS) and better response to TMZ-based radio-chemotherapy.GBM stem cells with this SNP showed lower levels of SEL1L expression and enhanced sensitivity to VPA.

View Article: PubMed Central - PubMed

Affiliation: Neuro-Bio-Oncology Center/Policlinico di Monza Foundation, Vercelli 13100, Italy.

ABSTRACT
The suppressor of Lin-12-like (C. elegans) (SEL1L) is involved in the endoplasmic reticulum (ER)-associated degradation pathway, malignant transformation and stem cells. In 412 formalin-fixed and paraffin-embedded brain tumors and 39 Glioblastoma multiforme (GBM) cell lines, we determined the frequency of five SEL1L single nucleotide genetic variants with regulatory and coding functions by a SNaPShot™ assay. We tested their possible association with brain tumor risk, prognosis and therapy. We studied the in vitro cytotoxicity of valproic acid (VPA), temozolomide (TMZ), doxorubicin (DOX) and paclitaxel (PTX), alone or in combination, on 11 GBM cell lines, with respect to the SNP rs12435998 genotype. The SNP rs12435998 was prevalent in anaplastic and malignant gliomas, and in meningiomas of all histologic grades, but unrelated to brain tumor risks. In GBM patients, the SNP rs12435998 was associated with prolonged overall survival (OS) and better response to TMZ-based radio-chemotherapy. GBM stem cells with this SNP showed lower levels of SEL1L expression and enhanced sensitivity to VPA.

No MeSH data available.


Related in: MedlinePlus