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

Marta Mellai, Monica Cattaneo, Alessandra Maria Storaci, Laura Annovazzi, Paola Cassoni, Antonio Melcarne, Pasquale De Blasio, Davide Schiffer, Ida Biunno

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)12452-12467
Number of pages16
Issue number14
Publication statusPublished - 2015


  • Brain tumors
  • Genetic variant
  • Glioblastoma multiforme
  • Prognosis
  • SEL1L

ASJC Scopus subject areas

  • Oncology


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