The right to deduct the input tax with no option to correct the tax return owing to the expiry of the tax obligation

Podatnik nie może legalnie stosować poglądu wynikającego z interpretacji prawa krajowego, który zaprzeczałby istocie podatku od wartości dodanej wynikającej z prawa UE i nie odpowiadałby zasadniczym jego cechom. Teza, jakoby podatnik, mając zamiar pomniejszyć podatek należny o podatek naliczony, musiałby ponownie (po raz drugi) wykazać podatek należny, byłaby równoznaczna z zastosowaniem odmiennej stawki podatku niż ta, którą stosują inni podatnicy dokonujący analogicznych dostaw. Stosowanie zróżnicowanych stawek w stosunku do tych samych czynności – dostaw energii elektrycznej i gazu ziemnego spowodowałoby ponadto zakłócenie konkurencji, biorąc pod uwagę fakt, że inni przedsiębiorcy z tytułu tych samych czynności stosują stawkę 23%. Możliwości selektywnego zastosowania stawki niższej w stosunku do innych podmiotów przy założeniu, że podatnik powinien opodatkować dokonane czynności de facto według stawki 46%, kłóciłaby się z regułami konkurowania podmiotów gospodarczych na tych samych zasadach.The taxpayer must not legally apply a view, ensuing from interpretation of the national laws, which would oppose the essence of the value-added tax under the EU laws and would not be correspondent with its basic characteristics. The argument that, in an intent to have the output tax reduced by the input tax, the taxpayer would have to disclose the output tax once again, would be tantamount to application of a tax rate different to the one applied by other taxpayers who perform analogous supplies. Application of diverse rates to the same actions–supplies of electricity and natural gas–would moreover result in distorted competition, taking into account that the other entrepreneurs use the rate of 23% in respect of the same actions. A possibility to selectively apply a lower rate, in the context of those used by the other entities and given the assumption that the taxpayer ought to tax the actions performed, de facto, at the rate 46%, would conflict with the rules of competition between economic entities under the same rules

A case study of an integrative genomic and experimental therapeutic approach for rare tumors: identification of vulnerabilities in a pediatric poorly differentiated carcinoma

Abstract Background Precision medicine approaches are ideally suited for rare tumors where comprehensive characterization may have diagnostic, prognostic, and therapeutic value. We describe the clinical case and molecular characterization of an adolescent with metastatic poorly differentiated carcinoma (PDC). Given the rarity and poor prognosis associated with PDC in children, we utilized genomic analysis and preclinical models to validate oncogenic drivers and identify molecular vulnerabilities. Methods We utilized whole exome sequencing (WES) and transcriptome analysis to identify germline and somatic alterations in the patient’s tumor. In silico and in vitro studies were used to determine the functional consequences of genomic alterations. Primary tumor was used to generate a patient-derived xenograft (PDX) model, which was used for in vivo assessment of predicted therapeutic options. Results WES revealed a novel germline frameshift variant (p.E1554fs) in APC, establishing a diagnosis of Gardner syndrome, along with a somatic nonsense (p.R790*) APC mutation in the tumor. Somatic mutations in TP53, MAX, BRAF, ROS1, and RPTOR were also identified and transcriptome and immunohistochemical analyses suggested hyperactivation of the Wnt/ß-catenin and AKT/mTOR pathways. In silico and biochemical assays demonstrated that the MAX p.R60Q and BRAF p.K483E mutations were activating mutations, whereas the ROS1 and RPTOR mutations were of lower utility for therapeutic targeting. Utilizing a patient-specific PDX model, we demonstrated in vivo activity of mTOR inhibition with temsirolimus and partial response to inhibition of MEK. Conclusions This clinical case illustrates the depth of investigation necessary to fully characterize the functional significance of the breadth of alterations identified through genomic analysis

Additional file 1: Figure S1. of A case study of an integrative genomic and experimental therapeutic approach for rare tumors: identification of vulnerabilities in a pediatric poorly differentiated carcinoma

Activation of mTOR pathway in patient tumor sample. Figure S2 A. Levels of in vitro translated MAX, MAXR60Q, C-MYC, and MXD1 in samples used for EMSA. B Modeling BRAF kinase domain complexed with ATP and Mg2+. Figure S3. Validation of PDX tumor model by Sanger sequencing. Figure S4. Tumor response to selumetinib. (PDF 7254 kb