Reference Detail

Ref Type Journal Article
PMID (24356817)
Authors Bailey ML, O'Neil NJ, van Pel DM, Solomon DA, Waldman T, Hieter P
Title Glioblastoma cells containing mutations in the cohesin component STAG2 are sensitive to PARP inhibition.
Journal Molecular cancer therapeutics
Vol 13
Issue 3
Date 2014 Mar
URL
Abstract Text Recent data have identified STAG2, a core subunit of the multifunctional cohesin complex, as a highly recurrently mutated gene in several types of cancer. We sought to identify a therapeutic strategy to selectively target cancer cells harboring inactivating mutations of STAG2 using two independent pairs of isogenic glioblastoma cell lines containing either an endogenous mutant STAG2 allele or a wild-type STAG2 allele restored by homologous recombination. We find that mutations in STAG2 are associated with significantly increased sensitivity to inhibitors of the DNA repair enzyme PARP. STAG2-mutated, PARP-inhibited cells accumulated in G2 phase and had a higher percentage of micronuclei, fragmented nuclei, and chromatin bridges compared with wild-type STAG2 cells. We also observed more 53BP1 foci in STAG2-mutated glioblastoma cells, suggesting that these cells have defects in DNA repair. Furthermore, cells with mutations in STAG2 were more sensitive than cells with wild-type STAG2 when PARP inhibitors were used in combination with DNA-damaging agents. These data suggest that PARP is a potential target for tumors harboring inactivating mutations in STAG2, and strongly recommend that STAG2 status be determined and correlated with therapeutic response to PARP inhibitors, both prospectively and retrospectively, in clinical trials.

Filtering

  • Case insensitive filtering will display rows where any text in any cell matches the filter term
  • Simple literal full or partial string matches
  • Separate multiple filter terms with a spaces, order doesn't matter (a b c and c b a are equivalent )
  • Filtering will only apply to rows that are already loaded on the page, filtering has no impact on query parameters
  • Use quotes to match a longer phrase which contains spaces "mtor c1483f"

Sorting

  • Generally, the default sort order for tables is set to be first column ascending, however, specific tables may set a different default sort order.
  • Click on any column header arrows to sort by that column
  • Hold down the Shift key and click multiple columns to sort by more than one column, be sure to set ascending or descending order for a given column, before moving on to the next column.

Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Therapy Description
Drug Name Trade Name Synonyms Drug Classes Drug Description
Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
STAG2 S653* glioblastoma multiforme sensitive Olaparib Preclinical - Cell culture Actionable In a preclinical study, a glioblastoma cell line harboring a STAG2 mutation (reported as STAG2 S653*, PMID: 21852505) demonstrated increased sensitivity to treatment with Lynparza (olaparib) in culture compared to isogenic cells with wild-type STAG2 (PMID: 24356817). 21852505 24356817
STAG2 N357fs glioblastoma multiforme sensitive Olaparib Preclinical - Cell culture Actionable In a preclinical study, a glioblastoma cell line harboring a STAG2 mutation (reported as STAG2 N357fs, PMID: 21852505) demonstrated increased sensitivity to treatment with Lynparza (olaparib) in culture, resulting in decreased proliferation and colony formation, and increased DNA damage compared to isogenic cells with wild-type STAG2 (PMID: 24356817). 24356817
STAG2 N357fs glioblastoma multiforme sensitive Rucaparib Preclinical - Cell culture Actionable In a preclinical study, a glioblastoma cell line harboring a STAG2 mutation (reported as STAG2 N357fs, PMID: 21852505), demonstrated increased sensitivity to treatment with Rubraca (rucaparib) in culture compared to isogenic cells with wild-type STAG2 (PMID: 24356817). 21852505 24356817
STAG2 N357fs glioblastoma multiforme sensitive Veliparib Preclinical - Cell culture Actionable In a preclinical study, a glioblastoma cell line harboring a STAG2 mutation (reported as STAG2 N357fs, PMID: 21852505) demonstrated increased sensitivity to treatment with Veliparib (ABT-888) in culture compared to isogenic cells with wild-type STAG2 (PMID: 24356817). 21852505 24356817
STAG2 S653* glioblastoma multiforme sensitive Camptothecin Preclinical - Cell culture Actionable In a preclinical study, glioblastoma cells harboring a STAG2 mutation (reported as STAG2 S653*, PMID: 21852505) demonstrated increased sensitivity to the combination of Lynparza (olaparib) and camptothecin compared to isogenic cells with wild-type STAG2 in culture (PMID: 24356817). 24356817 21852505
STAG2 dec exp colorectal cancer sensitive Olaparib Preclinical Actionable In a preclinical study, colorectal cancer cells with knockdown of STAG2 expression demonstrated increased sensitivity to treatment with Lynparza (olaparib) in culture (PMID: 24356817). 24356817
STAG2 N357fs glioblastoma multiforme sensitive Olaparib + Temozolomide Preclinical - Cell culture Actionable In a preclinical study, glioblastoma cells harboring a STAG2 mutation (reported as STAG2 N357fs, PMID: 21852505) demonstrated increased sensitivity to the combination of Lynparza (olaparib) and Temodar (temozolomide) compared to isogenic cells with wild-type STAG2 in culture (PMID: 24356817). 21852505 24356817
STAG2 N357fs glioblastoma multiforme sensitive Camptothecin + Olaparib Preclinical - Cell culture Actionable In a preclinical study, glioblastoma cells harboring a STAG2 mutation (reported as STAG2 N357fs, PMID: 21852505) demonstrated increased sensitivity to the combination of Lynparza (olaparib) and camptothecin compared to isogenic cells with wild-type STAG2 in culture (PMID: 24356817). 21852505 24356817