Lab-grown Fallopian Tubes Reveal Ovarian Cancer's Origins

High-grade serous ovarian carcinoma usually begins with a precursor lesion known as Serous Tubal Intraepithelial Carcinoma (STIC) located in the fallopian tubes. These lesions universally harbour mutations in the TP53 gene, yet studying them has been difficult due to a lack of accurate laboratory models. Researchers have now bridged this gap by developing human fallopian tube epithelial organoids—miniature, 3D tissue structures—that mimic the disease.

Using CRISPR-Cas9 gene editing, the team generated organoids with a loss-of-function mutation in TP53. The resulting tissue successfully recapitulated key features of STIC lesions, including nuclear abnormalities, uncontrolled cell growth, and aneuploidy (an abnormal number of chromosomes). Furthermore, these organoids displayed a marked reduction in ciliated cells and a downregulation of DNA repair genes.

This genetic shift promoted a state conducive to carcinogenesis, confirming that the loss of p53 is a critical early event. This new model provides a valuable tool for studying the initial steps of ovarian cancer and developing strategies for early detection and prevention.