A comprehensive genomic analysis of nearly 400 endometrial tumors suggests that certain molecular characteristics—such as the frequency of mutations—could complement current pathology methods and help distinguish between principal types of endometrial tumors, as well as provide insights into potential treatment strategies. The study, led by investigators in The Cancer Genome Atlas (TCGA) Research Network and published in the journal Nature, revealed four novel tumor subtypes. Its findings represent the most comprehensive characterization of the molecular alterations in endometrial cancers available to date.
Clinically, endometrial cancers fall into two categories: endometrioid (type I) and serous (type II) tumors. Type I tumors are often treated with radiation therapy, given in addition to or after the primary treatment. Type II tumors are generally treated with chemotherapy. Distinguishing between different types of endometrial cancers is currently based on histology, but categorizing endometrial cancer tissues is often difficult.
In this study, investigators showed that approximately 25% of tumors classified as high-grade endometrioid showed frequent mutations in TP53, a tumor suppressor gene, as well as extensive copy number alterations. Both are key molecular characteristics associated with serous tumors, along with a small number of DNA methylation changes. Most endometrioid tumors, by contrast, have few copy number alterations or mutations in TP53, though there are frequent mutations in other well known cancer-associated genes, including PTEN, another tumor suppressor gene, and KRAS, a gene involved in regulating cell division.
The data suggest that some high grade endometrioid tumors have developed a similar pattern of alterations to serous tumors, and may benefit from a similar course of treatment. The new findings also may provide a roadmap for future clinical trials. Read the article.