TY - JOUR
T1 - SEL1L SNP rs 12435998, a predictor of glioblastoma survival and response to radio-chemotherapy
AU - Mellai, Marta
AU - Cattaneo, Monica
AU - Storaci, Alessandra Maria
AU - Annovazzi, Laura
AU - Cassoni, Paola
AU - Melcarne, Antonio
AU - Blasio, Pasquale De
AU - Schiffer, Davide
AU - Biunno, Ida
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
KW - Brain tumors
KW - Genetic variant
KW - Glioblastoma multiforme
KW - Prognosis
KW - SEL1L
UR - http://www.scopus.com/inward/record.url?scp=84930033325&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84930033325&partnerID=8YFLogxK
M3 - Article
AN - SCOPUS:84930033325
SN - 1949-2553
VL - 6
SP - 12452
EP - 12467
JO - Oncotarget
JF - Oncotarget
IS - 14
ER -