Exome sequencing identifies somatic gain-of-function PPM1D mutations in brainstem gliomas

This study led to the discovery of tumor-specific mutations in PPM1D, encoding wild-type p53–induced protein phosphatase 1D (WIP1), in 37.5% of the BSGs that harbored hallmark H3F3A mutations encoding p.Lys27Met substitutions. PPM1D mutations were mutually exclusive with TP53 mutations in BSG and attenuated p53 activation in vitro. PPM1D mutations were truncating alterations in exon 6 that enhanced the ability of PPM1D to suppress the activation of the DNA damage response checkpoint protein CHK2. These results define PPM1D as a frequent target of somatic mutation and as a potential therapeutic target in brainstem gliomas.

Source: Nature Genetics - June 1, 2014 Category: Genetics & Stem Cells Authors: Liwei ZhangLee H ChenHong WanRui YangZhaohui WangJie FengShaohua YangSiân JonesSizhen WangWeixin ZhouHuishan ZhuPatrick J KillelaJunting ZhangZhen WuGuilin LiShuyu HaoYu WangJoseph B WebbHenry S FriedmanAllan H FriedmanRoger E McLendonYiping HeZachary J Tags: Letter Source Type: research