Integrated genomic/epigenomic analysis stratifies subtypes of clear cell ovarian carcinoma, highlighting their cellular origin.

Autor: Nishijima, Akira, Oda, Katsutoshi, Hasegawa, Kosei, Koso, Takahiro, Asada, Kayo, Ikeda, Yuji, Taguchi, Ayumi, Maeda, Daichi, Nagae, Genta, Tsuji, Shingo, Tatsuno, Kenji, Uehara, Yuriko, Kurosaki, Akira, Sato, Sho, Tanikawa, Michihiro, Sone, Kenbun, Mori, Mayuyo, Ikemura, Masako, Fujiwara, Keiichi, Ushiku, Tetsuo
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Zdroj: Scientific Reports; 8/13/2024, Vol. 14 Issue 1, p1-13, 13p
Abstrakt: The cellular origin of clear cell ovarian carcinoma (CCOC), a major histological subtype of ovarian carcinoma remains elusive. Here, we explored the candidate cellular origin and identify molecular subtypes using integrated genomic/epigenomic analysis. We performed whole exome-sequencing, microarray, and DNA methylation array in 78 CCOC samples according to the original diagnosis. The findings revealed that ARID1A and/or PIK3CA mutations were mutually exclusive with DNA repair related genes, including TP53, BRCA1, and ATM. Clustering of CCOC and other ovarian carcinomas (n = 270) with normal tissues from the fallopian tube, ovarian surface epithelium, endometrial epithelium, and pelvic peritoneum mesothelium (PPM) in a methylation array showed that major CCOC subtypes (with ARID1A and/or PIK3CA mutations) were associated with the PPM-lile cluster (n = 64). This cluster was sub-divided into three clusters: (1) mismatch repair (MMR) deficient with tumor mutational burden-high (n = 2), (2) alteration of ARID1A (n = 51), and (3) ARID1A wild-type (n = 11). The remaining samples (n = 14) were subdivided into (4) ovarian surface epithelium-like (n = 11) and (5) fallopian tube-like (considered as high-grade serous histotype; n = 3). Among these, subtypes (1–3) and others (4 and 5) were found to be associated with immunoreactive signatures and epithelial-mesenchymal transition, respectively. These results contribute to the stratification of CCOC into biological subtypes. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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