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Whole-Exome Sequencing of Rare Site Endometriosis-Associated Cancer

Authors :
Sonomi Kurose
Kentaro Nakayama
Sultana Razia
Masako Ishikawa
Tomoka Ishibashi
Hitomi Yamashita
Seiya Sato
Asuka Sakiyama
Shinya Yoshioka
Misa Kobayashi
Satoru Nakayama
Yoshiro Otuski
Noriyoshi Ishikawa
Satoru Kyo
Source :
Diseases, Vol 9, Iss 1, p 14 (2021)
Publication Year :
2021
Publisher :
MDPI AG, 2021.

Abstract

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.

Details

Language :
English
ISSN :
20799721
Volume :
9
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Diseases
Publication Type :
Academic Journal
Accession number :
edsdoj.97120e9255c4a0f8bf9ea941647280a
Document Type :
article
Full Text :
https://doi.org/10.3390/diseases9010014