title: SEL1L SNP rs12435998, a predictor of glioblastoma survival and response to radio-chemotherapy.
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.
authors.affiliation: Neuro-Bio-Oncology Center/Policlinico di Monza Foundation, Vercelli 13100, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Mellai
authors.affiliation: Institute for Genetic and Biomedical Research, National Research Council, Milan 20138, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Cattaneo
authors.affiliation: Institute for Genetic and Biomedical Research, National Research Council, Milan 20138, Italy.
authors.forename: Alessandra Maria
authors.initials: AM
authors.lastname: Storaci
authors.affiliation: Neuro-Bio-Oncology Center/Policlinico di Monza Foundation, Vercelli 13100, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Annovazzi
authors.affiliation: Department of Medical Sciences, University of Turin/Città della Salute e della Scienza, Turin 10126, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Cassoni
authors.affiliation: Department of Neurosurgery, CTO Hospital/Città della Salute e della Scienza, Turin 10126, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Melcarne
authors.affiliation: ISENET Stem Cell Bank, Milan 20138, Italy.
authors.forename: Pasquale
authors.initials: P
authors.lastname: De Blasio
authors.affiliation: Neuro-Bio-Oncology Center/Policlinico di Monza Foundation, Vercelli 13100, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Schiffer
authors.affiliation: Institute for Genetic and Biomedical Research, National Research Council, Milan 20138, Italy.|IRCCS-Multimedica, Milan 20138, Italy.
authors.forename: Ida
authors.initials: I
authors.lastname: Biunno
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics*; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D059248:Chemoradiotherapy; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004317:Doxorubicin / Q000008:administration & dosage; D005838:Genotype; D005909:Glioblastoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D006801:Humans; D053208:Kaplan-Meier Estimate; D017239:Paclitaxel / Q000008:administration & dosage; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics*; D000077204:Temozolomide; D014635:Valproic Acid / Q000008:administration & dosage
chemical_list: D014408:Biomarkers, Tumor; D011506:Proteins; C117384:SEL1L protein, human; D014635:Valproic Acid; D003606:Dacarbazine; D004317:Doxorubicin; D017239:Paclitaxel; D000077204:Temozolomide
keywords: SEL1L; brain tumors; genetic variant; glioblastoma multiforme; prognosis