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Integrated genomic characterization of endometrial carcinoma

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  • Douglas A. Levine

    (Gynecology Service, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA.)

Abstract

We performed an integrated genomic, transcriptomic and proteomic characterization of 373 endometrial carcinomas using array- and sequencing-based technologies. Uterine serous tumours and ∼25% of high-grade endometrioid tumours had extensive copy number alterations, few DNA methylation changes, low oestrogen receptor/progesterone receptor levels, and frequent TP53 mutations. Most endometrioid tumours had few copy number alterations or TP53 mutations, but frequent mutations in PTEN, CTNNB1, PIK3CA, ARID1A and KRAS and novel mutations in the SWI/SNF chromatin remodelling complex gene ARID5B. A subset of endometrioid tumours that we identified had a markedly increased transversion mutation frequency and newly identified hotspot mutations in POLE. Our results classified endometrial cancers into four categories: POLE ultramutated, microsatellite instability hypermutated, copy-number low, and copy-number high. Uterine serous carcinomas share genomic features with ovarian serous and basal-like breast carcinomas. We demonstrated that the genomic features of endometrial carcinomas permit a reclassification that may affect post-surgical adjuvant treatment for women with aggressive tumours.

Suggested Citation

  • Douglas A. Levine, 2013. "Integrated genomic characterization of endometrial carcinoma," Nature, Nature, vol. 497(7447), pages 67-73, May.
    • Handle: RePEc:nat:nature:v:497:y:2013:i:7447:d:10.1038_nature12113
    DOI: 10.1038/nature12113
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    Cited by:

    1. Amirali Darbandsari & Hossein Farahani & Maryam Asadi & Matthew Wiens & Dawn Cochrane & Ali Khajegili Mirabadi & Amy Jamieson & David Farnell & Pouya Ahmadvand & Maxwell Douglas & Samuel Leung & Puran, 2024. "AI-based histopathology image analysis reveals a distinct subset of endometrial cancers," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    2. Olga Adamczyk-Gruszka & Agata Horecka-Lewitowicz & Jakub Gruszka & Monika Wawszczak-Kasza & Agnieszka Strzelecka & Piotr Lewitowicz, 2022. "Endometrial Cancer in Aspect of Forkhead Box Protein Contribution," IJERPH, MDPI, vol. 19(16), pages 1-7, August.
    3. Yanan Wang & Giovanni Chiappetta & Raphaël Guérois & Yijun Liu & Stéphane Romero & Daniel J. Boesch & Matthias Krause & Claire A. Dessalles & Avin Babataheri & Abdul I. Barakat & Baoyu Chen & Joelle V, 2023. "PPP2R1A regulates migration persistence through the NHSL1-containing WAVE Shell Complex," Nature Communications, Nature, vol. 14(1), pages 1-18, December.

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