Comparative Analysis of Genetic Alterations, HPV-Status, and PD-L1 Expression in Neuroendocrine Carcinomas of the Cervix
Neuroendocrine carcinoma of the cervix (NECC) is a rare and highly aggressive tumor with no efficient treatment. We examined genetic features of NECC and identified potential therapeutic targets. A total of 272 patients with cervical cancer (25 NECC, 180 squamous cell carcinoma, 53 adenocarcinoma, a...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-03-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/6/1215 |
| _version_ | 1797541859179888640 |
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| author | Daisuke Takayanagi Sou Hirose Ikumi Kuno Yuka Asami Naoya Murakami Maiko Matsuda Yoko Shimada Kuniko Sunami Masaaki Komatsu Ryuji Hamamoto Mayumi Kobayashi Kato Koji Matsumoto Takashi Kohno Tomoyasu Kato Kouya Shiraishi Hiroshi Yoshida |
| author_facet | Daisuke Takayanagi Sou Hirose Ikumi Kuno Yuka Asami Naoya Murakami Maiko Matsuda Yoko Shimada Kuniko Sunami Masaaki Komatsu Ryuji Hamamoto Mayumi Kobayashi Kato Koji Matsumoto Takashi Kohno Tomoyasu Kato Kouya Shiraishi Hiroshi Yoshida |
| author_sort | Daisuke Takayanagi |
| collection | DOAJ |
| description | Neuroendocrine carcinoma of the cervix (NECC) is a rare and highly aggressive tumor with no efficient treatment. We examined genetic features of NECC and identified potential therapeutic targets. A total of 272 patients with cervical cancer (25 NECC, 180 squamous cell carcinoma, 53 adenocarcinoma, and 14 adenosquamous carcinoma) were enrolled. Somatic hotspot mutations in 50 cancer-related genes were detected using the Ion AmpliSeq Cancer Hotspot Panel v2. Human papillomavirus (HPV)-positivity was examined by polymerase chain reaction (PCR)-based testing and in situ hybridization assays. Programmed cell death-ligand 1 (PD-L1) expression was examined using immunohistochemistry. Somatic mutation data for 320 cases of cervical cancer from the Project GENIE database were also analyzed. NECC showed similar (<i>PIK3CA</i>, 32%; <i>TP53</i>, 24%) and distinct (<i>SMAD4</i>, 20%; <i>RET</i>, 16%; <i>EGFR</i>, 12%; <i>APC</i>, 12%) alterations compared with other histological types. The GENIE cohort had similar profiles and <i>RB1</i> mutations in 27.6% of NECC cases. Eleven (44%) cases had at least one actionable mutation linked to molecular targeted therapies and 14 (56%) cases showed more than one combined positive score for PD-L1 expression. HPV-positivity was observed in all NECC cases with a predominance of HPV-18. We report specific gene mutation profiles for NECC, which can provide a basis for the development of novel therapeutic strategies. |
| first_indexed | 2024-03-10T13:21:37Z |
| format | Article |
| id | doaj.art-be265a731e9b414092eae0e162e521fd |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T13:21:37Z |
| publishDate | 2021-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-be265a731e9b414092eae0e162e521fd2023-11-21T09:58:00ZengMDPI AGCancers2072-66942021-03-01136121510.3390/cancers13061215Comparative Analysis of Genetic Alterations, HPV-Status, and PD-L1 Expression in Neuroendocrine Carcinomas of the CervixDaisuke Takayanagi0Sou Hirose1Ikumi Kuno2Yuka Asami3Naoya Murakami4Maiko Matsuda5Yoko Shimada6Kuniko Sunami7Masaaki Komatsu8Ryuji Hamamoto9Mayumi Kobayashi Kato10Koji Matsumoto11Takashi Kohno12Tomoyasu Kato13Kouya Shiraishi14Hiroshi Yoshida15Division of Genome Biology, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, JapanDepartment of Obstetrics and Gynecology, The Jikei University School of Medicine, 3-19-18, Nishishinbashi, Minato-ku, Tokyo 105-8471, JapanDivision of Genome Biology, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, JapanDivision of Genome Biology, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, JapanDepartment of Radiation Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, JapanDivision of Genome Biology, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, JapanDivision of Genome Biology, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, JapanDivision of Genome Biology, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, JapanDivision of Molecular Modification and Cancer Biology, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, JapanDivision of Molecular Modification and Cancer Biology, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, JapanDepartment of Gynecology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, JapanDepartment of Obstetrics and Gynecology, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8666, JapanDivision of Genome Biology, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, JapanDepartment of Gynecology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, JapanDivision of Genome Biology, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, JapanDepartment of Diagnostic Pathology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, JapanNeuroendocrine carcinoma of the cervix (NECC) is a rare and highly aggressive tumor with no efficient treatment. We examined genetic features of NECC and identified potential therapeutic targets. A total of 272 patients with cervical cancer (25 NECC, 180 squamous cell carcinoma, 53 adenocarcinoma, and 14 adenosquamous carcinoma) were enrolled. Somatic hotspot mutations in 50 cancer-related genes were detected using the Ion AmpliSeq Cancer Hotspot Panel v2. Human papillomavirus (HPV)-positivity was examined by polymerase chain reaction (PCR)-based testing and in situ hybridization assays. Programmed cell death-ligand 1 (PD-L1) expression was examined using immunohistochemistry. Somatic mutation data for 320 cases of cervical cancer from the Project GENIE database were also analyzed. NECC showed similar (<i>PIK3CA</i>, 32%; <i>TP53</i>, 24%) and distinct (<i>SMAD4</i>, 20%; <i>RET</i>, 16%; <i>EGFR</i>, 12%; <i>APC</i>, 12%) alterations compared with other histological types. The GENIE cohort had similar profiles and <i>RB1</i> mutations in 27.6% of NECC cases. Eleven (44%) cases had at least one actionable mutation linked to molecular targeted therapies and 14 (56%) cases showed more than one combined positive score for PD-L1 expression. HPV-positivity was observed in all NECC cases with a predominance of HPV-18. We report specific gene mutation profiles for NECC, which can provide a basis for the development of novel therapeutic strategies.https://www.mdpi.com/2072-6694/13/6/1215neuroendocrine carcinomascervical cancernext-generation sequencingtargeted therapyHPVPD-L1 |
| spellingShingle | Daisuke Takayanagi Sou Hirose Ikumi Kuno Yuka Asami Naoya Murakami Maiko Matsuda Yoko Shimada Kuniko Sunami Masaaki Komatsu Ryuji Hamamoto Mayumi Kobayashi Kato Koji Matsumoto Takashi Kohno Tomoyasu Kato Kouya Shiraishi Hiroshi Yoshida Comparative Analysis of Genetic Alterations, HPV-Status, and PD-L1 Expression in Neuroendocrine Carcinomas of the Cervix Cancers neuroendocrine carcinomas cervical cancer next-generation sequencing targeted therapy HPV PD-L1 |
| title | Comparative Analysis of Genetic Alterations, HPV-Status, and PD-L1 Expression in Neuroendocrine Carcinomas of the Cervix |
| title_full | Comparative Analysis of Genetic Alterations, HPV-Status, and PD-L1 Expression in Neuroendocrine Carcinomas of the Cervix |
| title_fullStr | Comparative Analysis of Genetic Alterations, HPV-Status, and PD-L1 Expression in Neuroendocrine Carcinomas of the Cervix |
| title_full_unstemmed | Comparative Analysis of Genetic Alterations, HPV-Status, and PD-L1 Expression in Neuroendocrine Carcinomas of the Cervix |
| title_short | Comparative Analysis of Genetic Alterations, HPV-Status, and PD-L1 Expression in Neuroendocrine Carcinomas of the Cervix |
| title_sort | comparative analysis of genetic alterations hpv status and pd l1 expression in neuroendocrine carcinomas of the cervix |
| topic | neuroendocrine carcinomas cervical cancer next-generation sequencing targeted therapy HPV PD-L1 |
| url | https://www.mdpi.com/2072-6694/13/6/1215 |
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