SEL1L  SNP rs12435998, 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

doi:10.18632/oncotarget.3611

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This article has been corrected. Correction in: Oncotarget. 2018; 9:32731.

SEL1L SNP rs12435998, 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 and Ida Biunno

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Oncotarget. 2015; 6:12452-12467. https://doi.org/10.18632/oncotarget.3611

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Abstract

Marta Mellai1,*, Monica Cattaneo2,*, Alessandra Maria Storaci2, Laura Annovazzi1, Paola Cassoni3, Antonio Melcarne4, Pasquale De Blasio6, Davide Schiffer1, Ida Biunno2,5

1Neuro-Bio-Oncology Center/Policlinico di Monza Foundation, Vercelli 13100, Italy

2Institute for Genetic and Biomedical Research, National Research Council, Milan 20138, Italy

3Department of Medical Sciences, University of Turin/Città della Salute e della Scienza, Turin 10126, Italy

4Department of Neurosurgery, CTO Hospital/Città della Salute e della Scienza, Turin 10126, Italy

5IRCCS-Multimedica, Milan 20138, Italy

6ISENET Stem Cell Bank, Milan 20138, Italy

*These authors have contributed equally to this work

Correspondence to:

Ida Biunno, e-mail: [email protected]

Keywords: brain tumors, glioblastoma multiforme, SEL1L, genetic variant, prognosis

Received: January 21, 2015 Accepted: March 14, 2015 Published: April 10, 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 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.

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

Abstract