## Registered report: Diverse somatic mutation patterns and pathway alterations in human cancers <br> **Abstract:** The [Reproducibility Project: Cancer Biology][1] seeks to address growing concerns about reproducibility in scientific research by conducting replications of selected experiments from a number of high-profile papers in the field of cancer biology. The papers, which were published between 2010 and 2012, were selected on the basis of [citations and Altmetric scores][2] ([Errington et al., 2014][3]). This Registered Report describes the proposed replication plan of key experiments from "Diverse somatic mutation patterns and pathway alterations in human cancers" by Kan and colleagues published in *Nature* in 2010 ([Kan et al., 2010][4]). The experiments to be replicated are those reported in Figures 3D-F and 4C-F. Kan and colleagues utilized mismatch repair detection (MRD) technology to identify somatic mutations in primary human tumor samples and identified a previously uncharacterized arginine 243 to histidine (R243H) mutation in the G-protein α subunit *GNAO1* in breast carcinoma tissue. In Figures 3D-F, Kan and colleagues demonstrated that stable expression of mutant *GNAO1^R243D* conferred a significant growth advantage in human mammary epithelial cells, confirming the oncogenic potential of this mutation. Similarly, expression of variants with somatic mutations in *MAP2K4*, a JNK pathway kinase (shown in Figures 4C-E) resulted in a significant increase in anchorage-independent growth. Interestingly, these mutants exhibited reduced kinase activity compared to wild type *MAP2K4*, indicating these mutations impose a dominant-negative influence to promote growth (Figure 4F). The Reproducibility Project: Cancer Biology is a collaboration between the [Center for Open Science][5] and [Science Exchange][6] and the results of the replications will be published in [*eLife*][7]. ---------- ### Contents This component contains additional materials relating to the Registered Report for Study 6: Kan et al., 2010, *Nature*. The Registered Report can be found [here][8]. ---------- **Registered Report Initial Draft**: - This document represents the first draft of the selected experimental protocols. It contains the information that the Core team, with help from scientist volunteers, was able to glean from the original publication and its supplemental materials before the original authors were contacted for their input. - [Study 6 Registered Report Initial Draft][9] **Power Calculations**: - These documents contain details about how power calculations were performed, and include spreadsheets documenting statistical tests as well as any PRISM files, R scripts, or additional materials used. - [Study 6 Power Calculations][10] - [Study 6 Protocol 5 Figure 4D 1-way ANOVA.R][11] - Study 6 Protocol 6 Figure 4F data estimation files: - [MAP2K4 input quant.jpg][12] - [MAP2K4 input quant results.xls][13] - [p-MBP quant.jpg][14] - [p-MBP quant results.xls][15] - [pJNK quant.jpg][16] - [pJNK quant results.xls][17] [1]: https://osf.io/e81xl/wiki/home/ [2]: https://osf.io/e81xl/wiki/studies/ [3]: https://doi.org/10.7554/eLife.04333 [4]: https://doi.org/10.1038/nature09208 [5]: http://centerforopenscience.org/ [6]: https://www.scienceexchange.com/ [7]: https://elifesciences.org/ [8]: https://elifesciences.org/articles/11566 [9]: https://osf.io/qtyhj/ [10]: https://osf.io/4be3y/ [11]: https://osf.io/crxak/ [12]: https://osf.io/sgf65/ [13]: https://osf.io/deuap/ [14]: https://osf.io/hvfu3/ [15]: https://osf.io/8qcxe/ [16]: https://osf.io/w96q8/ [17]: https://osf.io/epk5y/