Whole-Exome Sequencing of Rare Site Endometriosis-Associated Cancer
| Autor: | Yoshiro Otuski, Seiya Sato, Kentaro Nakayama, Misa Kobayashi, Sultana Razia, Satoru Nakayama, Sonomi Kurose, Tomoka Ishibashi, Shinya Yoshioka, Satoru Kyo, Masako Ishikawa, Noriyoshi Ishikawa, Hitomi Yamashita, Asuka Sakiyama |
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| Rok vydání: | 2020 |
| Předmět: |
ARID1A
lcsh:Medicine immune checkpoint inhibitor Article Malignant transformation Frameshift mutation 03 medical and health sciences 0302 clinical medicine Medicine PTEN Exome sequencing 030219 obstetrics & reproductive medicine Pilocytic astrocytoma biology business.industry lcsh:R Cancer medicine.disease actionable variants 030220 oncology & carcinogenesis Clear cell carcinoma Cancer research biology.protein rare site endometriosis-associated cancer business exome sequencing |
| Zdroj: | Diseases Volume 9 Issue 1 Diseases, Vol 9, Iss 14, p 14 (2021) |
| ISSN: | 2079-9721 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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