Editors' ChoiceOvarian Cancer

Searching for the ovarian cancer cell of origin

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Science Translational Medicine  01 Nov 2017:
Vol. 9, Issue 414, eaaq1227
DOI: 10.1126/scitranslmed.aaq1227

Abstract

Genomic analyses of ovarian cancer evolution suggest an origin in the fallopian tube.

Although there are several types of ovarian cancer, high-grade serous ovarian carcinomas are the most common. These cancers carry a poor prognosis and have historically been thought of as originating from the ovarian surface epithelium. However, several recent reports have raised the possibility that the fallopian tube epithelium is the actual origin of this deadly cancer, yet definitive evidence was lacking. To address this, Labidi-Galy and Papp et al. isolated laser capture microdissected cells from tumors ranging from early stages to metastases from nine patients. They used whole-exome sequencing and copy number analysis to map the origin and evolution of ovarian carcinomas.

Consistent with previous reports, p53 mutations were found to be one of the earliest events in the development of ovarian carcinomas. Importantly, although mutant p53 was found in every early lesion and tumor examined in the fallopian tube, it was never detected in the ovarian surface epithelium, thus providing evidence of the cancer’s origin in the fallopian tube. Using mathematical modeling, the authors concluded that the progression from an early fallopian tube premalignant lesion to ovarian cancer can be as short as 1.9 years and averages around 6.5 years. However, after the ovarian cancer is initiated, it takes on average only 2 years to develop metastases, which is fast compared with other cancers. This accelerated schedule of metastasis may be due to nearby amenable environments for the cells to colonize to, or the ability of many ovarian cancer cells to grow without attachment.

It is precisely its highly metastatic nature that makes ovarian cancer so deadly. Rarely diagnosed before the tumor cells have spread extensively throughout the peritoneum, it can be challenging to treat; its prevention therefore takes higher priority. These findings suggest that the surgical removal of fallopian tubes (salpingectomy) in women at high or even moderate risk may be effective in preventing carcinomas while sparing the ovaries, which are important producers of hormones that prevent coronary heart disease and other illnesses in older women.

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