Genome data set to sharpen endometrial cancer diagnosis and treatment

Findings from a recently completed comprehensive genomic analysis have the potential to complement current pathology methods used in endometrial cancer and help distinguish between principal types of endometrial tumors. The results also revealed genomic similarities between endometrial cancer and breast, ovarian, and colorectal cancers and uncovered four novel subtypes of endometrial tumors.

Researchers from the National Cancer Institute (NCI) Cancer Genome Atlas Research Network analyzed endometrial tumor samples from 373 patients using array- and sequencing-based technologies. They learned that approximately 25% of women with endometrial cancer who are thought to have high-grade endometrioid (type 1) tumors based on pathology findings actually have tumors that exhibit key molecular characteristics of serous (type II) tumors, which are associated with less favorable outcomes.

Radiation therapy is often used to combat type I tumors, whereas chemotherapy generally is used against type II tumors. According to an NCI statement, the new data suggest that some high-grade endometrioid tumors have developed a strikingly similar pattern of alterations to serous tumors, and may benefit from a similar course of treatment.

Endometrial serous carcinoma was also found to have some of the same genomic features as high-grade serous ovarian carcinomas and basal-like breast cancer: The three cancers share a high frequency of mutations in the tumor suppressor gene TP53 and a low frequency of mutations in the tumor suppressor gene PTEN.

The study group was surprised to find shared characteristics between endometrial and colorectal tumors, with both cancer types demonstrating a high frequency of microsatellite instability (where the repair mechanism for DNA is broken), and mutations in the POLE gene, which is involved in DNA replication and repair.

The identification of the four novel genomic-based subtypes of endometrial cancer may set the stage for new diagnostic and treatment approaches. “Developing therapies for each subtype independent of the other may improve outcomes, as has been shown in breast cancer,” noted study coleader Elaine Mardis, PhD, in the NCI statement. Mardis is codirector of the Genome Institute at Washington University School of Medicine in St. Louis, Missouri.

The full report of the analysis appears in the journal Nature (2013;497:67-73).

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