Patient-derived organoids from endometrial disease capture clinical heterogeneity and are amenable to drug screening

Nature Cell Biology
Matteo BorettoHugo Vankelecom

Abstract

Endometrial disorders represent a major gynaecological burden. Current research models fail to recapitulate the nature and heterogeneity of these diseases, thereby hampering scientific and clinical progress. Here we developed long-term expandable organoids from a broad spectrum of endometrial pathologies. Organoids from endometriosis show disease-associated traits and cancer-linked mutations. Endometrial cancer-derived organoids accurately capture cancer subtypes, replicate the mutational landscape of the tumours and display patient-specific drug responses. Organoids were also established from precancerous pathologies encompassing endometrial hyperplasia and Lynch syndrome, and inherited gene mutations were maintained. Endometrial disease organoids reproduced the original lesion when transplanted in vivo. In summary, we developed multiple organoid models that capture endometrial disease diversity and will provide powerful research models and drug screening and discovery tools.

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Datasets Mentioned

BETA
E-MTAB-7688

Methods Mentioned

BETA
surgical resection
biopsies
RNA-seq
PCR
biopsy
Feature Extraction
Smart-Seq

Software Mentioned

Samtools
GraphPad Prism
Ensemble
Burrows−Wheeler Aligner
mcf
ea
GATK
Hisat2
EM
Feature Extraction

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