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Whole-Exome Sequencing of Rare Site Endometriosis-Associated Cancer

Malignant transformation of extraovarian endometriosis is rare, with the carcinogenesis mechanism unclear. To clarify the actionable variants of rare-site endometriosis-associated cancer (RSEAC), we performed whole-exome sequencing for the tumor, in two patients. The intestine was affected in both c...

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Autores principales: Kurose, Sonomi, Nakayama, Kentaro, Razia, Sultana, Ishikawa, Masako, Ishibashi, Tomoka, Yamashita, Hitomi, Sato, Seiya, Sakiyama, Asuka, Yoshioka, Shinya, Kobayashi, Misa, Nakayama, Satoru, Otuski, Yoshiro, Ishikawa, Noriyoshi, Kyo, Satoru
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7931088/
https://www.ncbi.nlm.nih.gov/pubmed/33557369
http://dx.doi.org/10.3390/diseases9010014
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author Kurose, Sonomi
Nakayama, Kentaro
Razia, Sultana
Ishikawa, Masako
Ishibashi, Tomoka
Yamashita, Hitomi
Sato, Seiya
Sakiyama, Asuka
Yoshioka, Shinya
Kobayashi, Misa
Nakayama, Satoru
Otuski, Yoshiro
Ishikawa, Noriyoshi
Kyo, Satoru
author_facet Kurose, Sonomi
Nakayama, Kentaro
Razia, Sultana
Ishikawa, Masako
Ishibashi, Tomoka
Yamashita, Hitomi
Sato, Seiya
Sakiyama, Asuka
Yoshioka, Shinya
Kobayashi, Misa
Nakayama, Satoru
Otuski, Yoshiro
Ishikawa, Noriyoshi
Kyo, Satoru
author_sort Kurose, Sonomi
collection PubMed
description Malignant transformation of extraovarian endometriosis is rare, with the carcinogenesis mechanism unclear. To clarify the actionable variants of rare-site endometriosis-associated cancer (RSEAC), we performed whole-exome sequencing for the tumor, in two patients. The intestine was affected in both cases, although the histology was that of clear cell carcinoma and undifferentiated carcinoma, respectively. Therefore, the cases were referred to as endometriosis-associated intestinal tumors (EIATs). Actionable variants (all frameshift mutations) were identified in tumor suppressor genes ARID1A, PTEN, and p53; however, no oncogenic variants were identified. Both cases were microsatellite stable. The patient with undifferentiated carcinoma exhibited hypermutator and homologous recombination deficiency phenotypes. The dominant mutation signatures were signature 30 (small subset of breast cancers) and 19 (pilocytic astrocytoma) in patient 1, and signature 5 (small subset of breast cancers) and 3 (breast, ovarian, and pancreatic cancers) in patient 2. Immunohistochemistry revealed positive CD8 and PD-1 expression in both patients; patient 1 also showed positive PDL-1 expression. Our results suggest that RSEAC is associated with variants of tumor suppressor genes as epigenetic alterations. Mutation signature-based whole-exome sequencing could be useful to select an adjuvant chemotherapy regimen. High CD8 and PD-1 expression in RSEAC suggests that immune checkpoint inhibitors are useful for treatment.
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spelling pubmed-79310882021-03-05 Whole-Exome Sequencing of Rare Site Endometriosis-Associated Cancer Kurose, Sonomi Nakayama, Kentaro Razia, Sultana Ishikawa, Masako Ishibashi, Tomoka Yamashita, Hitomi Sato, Seiya Sakiyama, Asuka Yoshioka, Shinya Kobayashi, Misa Nakayama, Satoru Otuski, Yoshiro Ishikawa, Noriyoshi Kyo, Satoru Diseases Article Malignant transformation of extraovarian endometriosis is rare, with the carcinogenesis mechanism unclear. To clarify the actionable variants of rare-site endometriosis-associated cancer (RSEAC), we performed whole-exome sequencing for the tumor, in two patients. The intestine was affected in both cases, although the histology was that of clear cell carcinoma and undifferentiated carcinoma, respectively. Therefore, the cases were referred to as endometriosis-associated intestinal tumors (EIATs). Actionable variants (all frameshift mutations) were identified in tumor suppressor genes ARID1A, PTEN, and p53; however, no oncogenic variants were identified. Both cases were microsatellite stable. The patient with undifferentiated carcinoma exhibited hypermutator and homologous recombination deficiency phenotypes. The dominant mutation signatures were signature 30 (small subset of breast cancers) and 19 (pilocytic astrocytoma) in patient 1, and signature 5 (small subset of breast cancers) and 3 (breast, ovarian, and pancreatic cancers) in patient 2. Immunohistochemistry revealed positive CD8 and PD-1 expression in both patients; patient 1 also showed positive PDL-1 expression. Our results suggest that RSEAC is associated with variants of tumor suppressor genes as epigenetic alterations. Mutation signature-based whole-exome sequencing could be useful to select an adjuvant chemotherapy regimen. High CD8 and PD-1 expression in RSEAC suggests that immune checkpoint inhibitors are useful for treatment. MDPI 2021-02-04 /pmc/articles/PMC7931088/ /pubmed/33557369 http://dx.doi.org/10.3390/diseases9010014 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kurose, Sonomi
Nakayama, Kentaro
Razia, Sultana
Ishikawa, Masako
Ishibashi, Tomoka
Yamashita, Hitomi
Sato, Seiya
Sakiyama, Asuka
Yoshioka, Shinya
Kobayashi, Misa
Nakayama, Satoru
Otuski, Yoshiro
Ishikawa, Noriyoshi
Kyo, Satoru
Whole-Exome Sequencing of Rare Site Endometriosis-Associated Cancer
title Whole-Exome Sequencing of Rare Site Endometriosis-Associated Cancer
title_full Whole-Exome Sequencing of Rare Site Endometriosis-Associated Cancer
title_fullStr Whole-Exome Sequencing of Rare Site Endometriosis-Associated Cancer
title_full_unstemmed Whole-Exome Sequencing of Rare Site Endometriosis-Associated Cancer
title_short Whole-Exome Sequencing of Rare Site Endometriosis-Associated Cancer
title_sort whole-exome sequencing of rare site endometriosis-associated cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7931088/
https://www.ncbi.nlm.nih.gov/pubmed/33557369
http://dx.doi.org/10.3390/diseases9010014
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