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Oncogenic mutations in PIK3CA, which encodes the phosphoinositide-3-kinase (PI3K) catalytic subunit p110α, occur in ∼25% of human breast cancers. In this study, we report the development of a knock-in mouse model for breast cancer where the endogenous Pik3ca allele was modified to allow tissue-specific conditional expression of a frequently found Pik3ca(H1047R) (Pik3ca(e20H1047R)) mutant allele. We found that activation of the latent Pik3ca(H1047R) allele resulted in breast tumors with multiple histological types. Whole-exome analysis of the Pik3ca(H1047R)-driven mammary tumors identified multiple mutations, including Trp53 mutations that appeared spontaneously during the development of adenocarinoma and spindle cell tumors. Further, we used this model to test the efficacy of GDC-0941, a PI3K inhibitor, in clinical development, and showed that the tumors respond to PI3K inhibition.
Pubmed ID: 22370636 RIS Download
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Software tool which predicts possible impact of amino acid substitution on structure and function of human protein using straightforward physical and comparative considerations. PolyPhen-2 is new development of PolyPhen tool for annotating coding nonsynonymous SNPs.
View all literature mentionsSoftware for analysis of array CGH data: detection of breakpoints in genomic profiles and assignment of a status (gain, normal or loss) to each chromosomal regions identified.
View all literature mentionsSoftware for Next-Generation DNA sequencing, Sanger DNA analysis, and RNA sequencing. It contains sequence analysis tools which include reference-guided alignments, de novo assembly, variant calling, and SNP analyses. It has integrated the Cufflinks suite for in-depth transcript analysis and differential gene expression of RNA-Seq data.
View all literature mentionsSoftware package for the analysis of gene expression microarray data, especially the use of linear models for analyzing designed experiments and the assessment of differential expression.
View all literature mentionsSoftware that automatically reads and processes up to 100 raw microarray image files. The software finds and places microarray grids, rejects outlier pixels, accurately determines feature intensities and ratios, flags outlier pixels, and calculates statistical confidences.
View all literature mentionsData analysis, graphing, and management application that allows users to import, manipulate, analyze data, and create customized plots. Plots include x-y probability, histogram, box, percentile, horizontal bar, stack bar, column, stack column, polar, and pie. Binned data can be exported to a histogram, step plot, or spike plot. KaleidaGraph works with Windows and Macintosh systems.
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
View all literature mentionsMus musculus with name STOCK Tg(MMTV-cre)4Mam/J from IMSR.
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