Erratum: PiggyBac mutagenesis and exome sequencing identify genetic driver landscapes and potential therapeutic targets of EGFR-mutant gliomas (Genome Biol (2020) 21 (181) DOI: 10.1186/s13059-020-02092-2)

Imran Noorani, Jorge De La Rosa, Yoon Ha Choi, Alexander Strong, Hannes Ponstingl, M. S. Vijayabaskar, Jusung Lee, Eunmin Lee, Angela Richard-Londt, Mathias Friedrich, Federica Furlanetto, Rocio Fuente, Ruby Banerjee, Fengtang Yang, Frances Law, Colin Watts, Roland Rad, George Vassiliou, Jong Kyoung Kim, Thomas SantariusSebastian Brandner, Allan Bradley

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Abstract

Following publication of the original paper [1], the authors identified errors the paper. Under the heading Whole-Exome Sequencing Reveals The Mutational Landscape in the results section, the following text has been updated. The updated text is displayed in bold typeface. In contrast to the relatively small number of recurrent mutations, EGFR-mutant tumors had complex genomes by DNA copy number analysis (Fig. 2b). Significant focal amplifications and deletions, identified by GISTIC2 35, were evident in regions with known cancer genes, for example significant focal Cdkn2a deletions (GISTIC qvalue = 1.39 × 10- 5 ) were evident and EGFRvIII (in Col1a1 locus, GISTIC q-value = 0.017) was recurrently amplified. Significantly recurrent focal deletions were present in a novel putative glioma driver Adgrl2 (GISTIC q-value = 2.19 × 10- 6 , Additional File 4: Table S3). Although focal deletions in Nlrp1b were present, recent evidence suggests these represent a strain-specific germline variant rather than being oncogenic [2]. Several of the most significantly mutated genes were also in regions with frequent deletions, including Trp53, Tead2 and Uimc1, supporting putative tumor suppressive roles (Fig. 3i). The caption of Fig. 3 has also been updated. The correct caption is supplied below. The updated text is displayed in bold typeface.Figure 3. Conditional PiggyBac transposon mutagenesis substitutes for genomic instability in EGFRvIII-mutant gliomas. A. Mouse constructs for PiggyBac transposition. The ATP1-S2 transposon line, with 20 copies per cell. Conditional PiggyBac transposase targeted to Rosa26 (tissue-specific PiggyBac transposase, TSPB), SA = splice acceptor; SD = splice donor; CAG = CAG promoter; SB = Sleeping Beauty; PB = PiggyBac inverted repeats; iPBase = insect version of the PiggyBac transposase. The transposon can activate gene transcription if it inserts in the same orientation as the gene, usually in a 5' position. Gene inactivation can occur if the transposon inserts in the body of the gene as a consequence of gene trapping which can occur in either orientation because of the presence of two splice acceptors and bidirectional poly(A) (pA) sites. B. Outline of the experimental design: quadruple transgenic mice conditionally activate EGFRvIII expression and PiggyBac transposition in the central nervous system. Resultant tumors are examined molecularly by whole-exome sequencing and mapping of transposon insertions. C. Histology of EGFRvIII-PB tumors; although not statistically significant, a higher proportion of grade IV brain tumors are observed compared with tumors lacking transposition. D. Immunostaining profile of a typical grade III brain glioma from an EGFRvIII-PB mouse, showing strong expression of neural stem and transit-amplifying cell markers. Scale bar corresponds to 2.8 mm for top panel, and 200 µm for all other panels. E. Representative karyotype of EGFRvIII-only and EGFRvIII-PB brain tumors, showing polyploidy in the non-PB tumor. F. Chromosomal aberrations in EGFRvIII-only and EGFRvIII-PB tumors (n = 3 and n = 5 tumors respectively; mean chromosomal aberrations 19 vs 6.4, p = 0.013, unpaired twotailed t-test; plots show mean +/- standard deviation). G. Copy number profile of EGFRvIII-PB tumors (n = 20) with focal amplifications and deletions in key genes highlighted. H. Mutational profile of 20 EGFRvIII-PB brain and spinal tumors from whole-exome sequencing. I. Key genes identified in gliomas, either as significantly mutated from MuSiC or copy number altered from GISTIC2, across all mouse brain and spinal tumors in both cohorts (note Nlrp1b deletions are however a germline variant [2]); each column represent one tumor. In addition, the authors identified an error in the author name of Yoon Ha Choi. The incorrect author name is: Yoonha Choi The correct author name is: Yoon Ha Choi.

Original languageEnglish
Article number206
JournalGenome Biology
Volume21
Issue number1
DOIs
StatePublished - 17 Aug 2020
Externally publishedYes

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