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. 2019 Oct 9;9:14476. doi: 10.1038/s41598-019-50891-w

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© The Author(s) 2019

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Protein domain structure of genes commonly mutated in LTTs. Overview of the domain structures of (a) ATP7B, (b) NRXN2 (Neurexin-2), (c) FAM205A, and (d) HECW1 (NEDL1). Mutations found in the TCGA data set as annotated from cBioportal and mutations found in LTTs were included. All mutations in the LTTs are missense mutations except for one FAM205A mutation in RT-112 (Table S14). (e) ATP7B mRNA expression was measured by qRT-PCR in parental UCCs and LTTs after treatment with siRNA against ATP7B or a non-targeting control. SDHA mRNA was used as a reference. (f) Relative cell viability after 48 h cisplatin treatment as measured by CellTiterGlo assay in parental UCCs and LTTs transfected with siRNA targeting ATP7B or a non-targeting negative control siRNA. Values represent the mean ± SD of biological quadruplicates, *p < 0.05 compared to non-targeting control. HECT: Homologous to the E6-AP Carboxyl Terminus; HECWN: HECTW1 N-terminal domain; H: Helical bundle; C2: C2 domain; WW: WW domain; HMA: Heavy metal-associated domain.