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Poly ADP‐ribose polymerase‐1 as a potential therapeutic target in Merkel cell carcinoma
Author(s) -
Ferrarotto Renata,
Cardnell Robert,
Su Shirley,
Diao Lixia,
Eterovic A. Karina,
Prieto Victor,
Morrisson William H.,
Wang Jing,
Kies Merrill S.,
Glisson Bonnie S.,
Byers Lauren Averett,
Bell Diana
Publication year - 2018
Publication title -
head and neck
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.012
H-Index - 127
eISSN - 1097-0347
pISSN - 1043-3074
DOI - 10.1002/hed.25146
Subject(s) - merkel cell carcinoma , olaparib , merkel cell polyomavirus , merkel cell , cancer research , biology , poly adp ribose polymerase , dna damage , carcinoma , polymerase , gene , dna , genetics
Background Patients with metastatic Merkel cell carcinoma are treated similarly to small cell lung cancer (SCLC). Poly ADP‐ribose polymerase‐1 (PARP1) is overexpressed in SCLC and response to PARP inhibitors have been reported in patients with SCLC. Our study explores PARP as a therapeutic target in Merkel cell carcinoma. Methods We evaluated PARP1 expression and Merkel cell polyomavirus (MCPyV) in 19 patients with Merkel cell carcinoma. Target exome‐sequencing was performed in 14 samples. Sensitivity to olaparib was tested in 4 Merkel cell carcinoma cell lines. Results Most Merkel cell carcinomas (74%) express PARP1 at high levels. Mutations in DNA‐damage repair genes were identified in 9 samples (64%), occurred exclusively in head neck primaries, and correlated with TP53/RB1 mutations. The TP53 / RB1 mutations were more frequent in MCPyV‐negative tumors. Sensitivity to olaparib was seen in the Merkel cell carcinoma line with highest PARP1 expression. Conclusion Based on PARP1 overexpression, DNA‐damage repair gene mutations, platinum sensitivity, and activity of olaparib in a Merkel cell carcinoma line, clinical trials with PARP inhibitors are warranted in Merkel cell carcinoma.