Prevalence of APC and PTEN Alterations in Urachal Cancer
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Prevalence of APC and PTEN Alterations in Urachal Cancer. / Nagy, Nikolett; Reis, Henning; Hadaschik, Boris; Niedworok, Christian; Módos, Orsolya; Szendrői, Attila; Bíró, Krisztina; Hager, Thomas; Herold, Thomas; Ablat, Jason; Black, Peter C; Okon, Krzysztof; Tolkach, Yuri; Csizmarik, Anita; Oláh, Csilla; Keresztes, David; Bremmer, Felix; Gaisa, Nadine T; Kriegsmann, Joerg; Kovalszky, Ilona; Kiss, András; Tímár, József; Szász, Marcell A; Rink, Michael; Fisch, Margit; Nyirády, Péter; Szarvas, Tibor.
in: PATHOL ONCOL RES, Jahrgang 26, Nr. 4, 10.2020, S. 2773-2781.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Prevalence of APC and PTEN Alterations in Urachal Cancer
AU - Nagy, Nikolett
AU - Reis, Henning
AU - Hadaschik, Boris
AU - Niedworok, Christian
AU - Módos, Orsolya
AU - Szendrői, Attila
AU - Bíró, Krisztina
AU - Hager, Thomas
AU - Herold, Thomas
AU - Ablat, Jason
AU - Black, Peter C
AU - Okon, Krzysztof
AU - Tolkach, Yuri
AU - Csizmarik, Anita
AU - Oláh, Csilla
AU - Keresztes, David
AU - Bremmer, Felix
AU - Gaisa, Nadine T
AU - Kriegsmann, Joerg
AU - Kovalszky, Ilona
AU - Kiss, András
AU - Tímár, József
AU - Szász, Marcell A
AU - Rink, Michael
AU - Fisch, Margit
AU - Nyirády, Péter
AU - Szarvas, Tibor
PY - 2020/10
Y1 - 2020/10
N2 - 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.
AB - 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.
U2 - 10.1007/s12253-020-00872-6
DO - 10.1007/s12253-020-00872-6
M3 - SCORING: Journal article
C2 - 32754865
VL - 26
SP - 2773
EP - 2781
JO - PATHOL ONCOL RES
JF - PATHOL ONCOL RES
SN - 1219-4956
IS - 4
ER -