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 includingAPCandPTENin 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.APCandPTENgenes
were affected in 15% (5/34) and 6% (2/34) of cases. Two of fiveAPCalterations (p.Y1075*,
p.K1199*) were truncating pathogenic mutations. One of the twoPTENvariants 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 ofAPCmutations in UrC represents a characteristic difference
to CRC. Based onAPCand 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.
