Poly ADP-ribose polymerase-1 as a potential therapeutic target in Merkel cell carcinoma

Renata Ferrarotto; Robert Cardnell; Shirley Su; Lixia Diao; A. Karina Eterovic; Victor Prieto; William H. Morrisson; Jing Wang; Merrill S. Kies; Bonnie S. Glisson; Lauren Averett Byers; Diana Bell

doi:10.1002/hed.25146

Poly ADP-ribose polymerase-1 as a potential therapeutic target in Merkel cell carcinoma

Renata Ferrarotto, Robert Cardnell, Shirley Su, Lixia Diao, A. Karina Eterovic, Victor Prieto, William H. Morrisson, Jing Wang, Merrill S. Kies, Bonnie S. Glisson, Lauren Averett Byers, Diana Bell

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10 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	1676-1684
Number of pages	9
Journal	Head and Neck
Volume	40
Issue number	8
DOIs	https://doi.org/10.1002/hed.25146
State	Published - Aug 2018

Keywords

Merkel cell carcinoma
Merkel cell polyomavirus
genomics
poly ADP-ribose polymerase (PARP)
targeted therapy

ASJC Scopus subject areas

Otorhinolaryngology

MD Anderson CCSG core facilities

Bioinformatics Shared Resource

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10.1002/hed.25146

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title = "Poly ADP-ribose polymerase-1 as a potential therapeutic target in Merkel cell carcinoma",

abstract = "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.",

keywords = "Merkel cell carcinoma, Merkel cell polyomavirus, genomics, poly ADP-ribose polymerase (PARP), targeted therapy",

author = "Renata Ferrarotto and Robert Cardnell and Shirley Su and Lixia Diao and Eterovic, {A. Karina} and Victor Prieto and Morrisson, {William H.} and Jing Wang and Kies, {Merrill S.} and Glisson, {Bonnie S.} and Byers, {Lauren Averett} and Diana Bell",

note = "Publisher Copyright: {\textcopyright} 2018 Wiley Periodicals, Inc.",

year = "2018",

month = aug,

doi = "10.1002/hed.25146",

language = "English (US)",

volume = "40",

pages = "1676--1684",

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publisher = "Wiley-Liss Inc.",

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T1 - Poly ADP-ribose polymerase-1 as a potential therapeutic target in Merkel cell carcinoma

AU - Ferrarotto, Renata

AU - Cardnell, Robert

AU - Su, Shirley

AU - Diao, Lixia

AU - Eterovic, A. Karina

AU - Prieto, Victor

AU - Morrisson, William H.

AU - Wang, Jing

AU - Kies, Merrill S.

AU - Glisson, Bonnie S.

AU - Byers, Lauren Averett

AU - Bell, Diana

PY - 2018/8

Y1 - 2018/8

N2 - 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.

AB - 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.

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KW - Merkel cell polyomavirus

KW - genomics

KW - poly ADP-ribose polymerase (PARP)

KW - targeted therapy

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Poly ADP-ribose polymerase-1 as a potential therapeutic target in Merkel cell carcinoma

Abstract

Keywords

ASJC Scopus subject areas

MD Anderson CCSG core facilities

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