Urachal carcinoma (UrC) is a rare tumor with remarkable histological and molecular similarities to colorectal cancer (CRC). Adenomatous polyposis coli (APC) is the most frequently affected gene in CRC, but the prevalence and significance of its alterations in UrC is poorly understood. In addition, loss of phosphatase and tensin homologue (PTEN) was shown to be associated with therapy resistance in CRC. Our primary aim was to assess specific genetic alterations including APC and PTEN in a large series of UrC samples in order to identify clinically significant genomic alterations. We analyzed a total of 40 UrC cases. Targeted 5-gene (APC, PTEN, DICER1, PRKAR1A, TSHR, WRN) panel sequencing was performed on the Illumina MiSeq platform (n = 34). In addition, ß-catenin (n = 38) and PTEN (n = 30) expressions were assessed by immunohistochemistry. APC and PTEN genes were affected in 15% (5/34) and 6% (2/34) of cases. Two of five APC alterations (p.Y1075*, p.K1199*) were truncating pathogenic mutations. One of the two PTEN variants was a pathogenic frameshift insertion (p.C211fs). In 29% (11/38) of samples, at least some weak nuclear ß-catenin immunostaining was detected and PTEN loss was observed in 20% (6/30) of samples. The low prevalence of APC mutations in UrC represents a characteristic difference to CRC. Based on APC and ß-catenin results, the Wnt pathway seems to be rarely affected in UrC. Considering the formerly described involvement of PTEN protein loss in anti-EGFR therapy-resistance its immunohistochemical testing may have therapeutic relevance.

脐尿管癌 (UrC) 是一种罕见的肿瘤，与结直肠癌 (CRC) 具有显着的组织学和分子相似性。腺瘤性结肠息肉病 ( APC)是 CRC 中最常受影响的基因，但其在 UrC 中改变的普遍性和意义却知之甚少。此外，磷酸酶和张力蛋白同源物 (PTEN) 的丢失被证明与 CRC 的治疗抵抗有关。我们的主要目的是评估大量 UrC 样本中的特定遗传改变，包括APC和PTEN，以识别具有临床意义的基因组改变。我们总共分析了 40 个 UrC 病例。靶向 5 基因（APC、PTEN、DICER1、PRKAR1A、TSHR、WRN）面板测序在 Illumina MiSeq 平台上进行（n  = 34)。此外，通过免疫组织化学评估了 ß-catenin ( n  = 38) 和 PTEN ( n  = 30) 的表达。APC和PTEN基因在 15% (5/34) 和 6% (2/34) 的病例中受到影响。五个APC改变中的两个（p.Y1075*、p.K1199*）正在截断致病突变。两种PTEN变体之一是致病性移码插入 (p.C211fs)。在 29% (11/38) 的样本中，至少检测到一些弱核 ß-catenin 免疫染色，并且在 20% (6/30) 的样本中观察到 PTEN 丢失。UrC中APC突变的低流行率代表了与 CRC 的特征差异。基于APC和 ß-catenin 结果，Wnt 通路似乎在 UrC 中很少受到影响。考虑到先前描述的 PTEN 蛋白丢失与抗 EGFR 治疗抗性有关，其免疫组织化学测试可能具有治疗相关性。