Elevated CXorf67 Expression in PFA Ependymomas Suppresses DNA Repair and Sensitizes to PARP Inhibitors.

Abstract:

:Ependymoma is the third most common pediatric tumor with posterior fossa group A (PFA) being its most aggressive subtype. Ependymomas are generally refractory to chemotherapies and thus lack any effective treatment. Here, we report that elevated expression of CXorf67 (chromosome X open reading frame 67), which frequently occurs in PFA ependymomas, suppresses homologous recombination (HR)-mediated DNA repair. Mechanistically, CXorf67 interacts with PALB2 and inhibits PALB2-BRCA2 interaction, thereby inhibiting HR repair. Concordantly, tumor cells with high CXorf67 expression levels show increased sensitivity to poly(ADP-ribose) polymerase (PARP) inhibitors, especially when combined with radiotherapy. Thus, our findings have revealed a role of CXorf67 in HR repair and suggest that combination of PARP inhibitors with radiotherapy could be an effective treatment option for PFA ependymomas.

journal_name

Cancer Cell

journal_title

Cancer cell

authors

Han J,Yu M,Bai Y,Yu J,Jin F,Li C,Zeng R,Peng J,Li A,Song X,Li H,Wu D,Li L

doi

10.1016/j.ccell.2020.10.009

subject

Has Abstract

pub_date

2020-12-14 00:00:00

pages

844-856.e7

issue

6

eissn

1535-6108

issn

1878-3686

pii

S1535-6108(20)30540-7

journal_volume

38

pub_type

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