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Mutations Discovered That May Affect Treatment Of Patients With Endometrial Cancer

A study from the Cancer Genome Atlas Research Network, led by the and the , report that mutations discovered in genes may directly impact treatment plans for women with aggressive , as well as the classification of tumors.

The study was published in the journal Nature.

The researchers performed an integrated analysis of endometrial cancer tumor samples from 373 patients using array- and sequencing-based technologies. Among their findings, two endometrial cancer tumor subtypes – uterine serous tumors and high-grade endometrioid tumors – shared several genetic mutations.

The researchers found that approximately 25 percent of tumors classified as high-grade endometrioid actually had genetic features similar to uterine serous carcinoma tumors, such as extensive copy number alterations and frequent mutations in the TP53 gene. The TP53 gene encodes for a tumor suppressor protein called p53. Moreover, uterine serous carcinomas shared genomic features with ovarian serous and basal-like breast carcinomas.

Early stage endometrioid tumors are often treated with adjuvant radiotherapy, while similarly staged serous tumors are treated with chemotherapy. Based on these compelling genetic similarities, the researchers note that clinicians should carefully consider treating copy number-altered endometrioid patients with chemotherapy rather than adjuvant radiotherapy and formally test such hypotheses in prospective clinical trials.

“Some of the results reported in this paper can change the way endometrial cancers are classified and provide opportunities to test new treatment protocols for patients with this cancer,” said Raju S. Kucherlapati, PhD, Paul C. Cabot Professor of Genetics and Professor of Medicine at Brigham and Women’s Hospital, and study author.

Further analysis and characterization of endometrial tumor subtypes also led the researchers to suggest a reclassification of endometrial cancers into four categories, as opposed to the current broad classification of two categories. The four categories are: POLE ultramutated, microsatellite instability hypermutated, copy number low, and copy number high.

“These findings suggest that a subset of endometrial tumors have distinct patterns of copy number alterations and mutations that do not correlate with traditional grade or make-up of tumor tissue,” said Kucherlapati. The Genome Characterization Center in The Cancer Genome Atlas headed by Kucherlapati conducted whole genome sequencing of the tumors and identified copy number variations and structural rearrangements in these tumors.

Endometrial cancer occurs in the lining of the uterus, and is the fourth most common malignancy among women in the United States, with an estimated 47,000 new cases and 8,000 deaths in 2012.


The Cancer Genome Atlas Research Network is a project led by the National Cancer Institute and the National Human Genome Research Institute. Its mission is to catalogue genetic mutations responsible for cancer, as well as utilize the latest genomic technologies to improve the ability to diagnose, treat and prevent cancer through a better understanding of the genetic basis of disease.

This research was supported by the National Institutes of Health (5U24CA143799-04, 5U24CA143835-04, 5U24CA143840-04, 5U24CA143843-04, 5U24CA143845-04, 5U24CA143848-04, 5U24CA143858-04, 5U24CA143866-04, 5U24CA143867-04, 5U24CA143882-04, 5U24CA143883-04, 5U24CA144025-04, U54HG003067, U54HG003079, and U54HG003273).

Brigham and Women’s Hospital