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 SNaPShotTM 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 rs 12435998 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.

SEL1L SNP rs 12435998, a predictor of glioblastoma survival and response to radio-chemotherapy / M. Mellai, M. Cattaneo, A.M. Storaci, L. Annovazzi, P. Cassoni, A. Melcarne, P.D. Blasio, D. Schiffer, I. Biunno. - In: ONCOTARGET. - ISSN 1949-2553. - 6:14(2015 May 20), pp. 12452-12467. [10.18632/oncotarget.3611]

SEL1L SNP rs 12435998, a predictor of glioblastoma survival and response to radio-chemotherapy

A.M. Storaci;
2015

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 SNaPShotTM 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 rs 12435998 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.
Brain tumors; Genetic variant; Glioblastoma multiforme; Prognosis; SEL1L; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Blotting, Western; Brain Neoplasms; Cell Line, Tumor; Dacarbazine; Doxorubicin; Genotype; Glioblastoma; Humans; Kaplan-Meier Estimate; Paclitaxel; Polymerase Chain Reaction; Proteins; Temozolomide; Valproic Acid; Chemoradiotherapy; Polymorphism, Single Nucleotide;
Settore MED/08 - Anatomia Patologica
20-mag-2015
10-apr-2015
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/922009
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