Molecular Mechanism of Carcinogenesis in Endometrial Cancer: Using Next Generation Sequencing Technology for Discovery of Prevention and Therapeutic Targets

Endometrial cancer remains the leading female genital tract malignancy in industrialized countries. In Taiwan, the incidence rose tremendously in the past 30 years from less than 100 patients per year to over one thousand per year. More importantly, according to the data from Department of Health in 2009, it became the second ranking of women’s cancer in Taiwan. The mechanism underlying this rare disease entity remains unclear. The WHO classification categorizes endometrial hyperplasia as simple hyperplasia (SH), complex (CH), simple atypical (SAH), or complex atypical (CAH) on the basis of architectural crowding and nuclear atypia. The severity of an endometrial hyperplasia reflects risk of endometrial carcinoma. According to Kurman et al., the risk of progression to carcinoma was less than 1% in simple hyperplasia. However, there are exceptions in patients with simple hyperplasia in whom the progression to endometrial cancer occurred in a short period of time. A list of seven such patients was found in our cancer databank. The major problem is diagnostic agreement for endometrial neoplasms is poor. This 3-year study aim to investigate the mechanism of transitions from SH/CH to endometrial cancer using next generation sequencing technology to sequence the coding regions and cDNA of the genome, measure transcriptome changes, and characterize the microRNAs. In the first and second year, we plan to perform exon array and miRNA array on 10 FFPE samples from patients with endometrial cancer diagnosed at endometrial curettage Chang Gung Memorial Hospital but no residual cancer was seen at definitive surgeries. Ten prospective new incident endometrial cancer cases and 10 patients with documented endometrial hyperplasia (out of the 50 with suspected endometrial hyperplasia before endometrial curettage who have signed informed consent) whose fresh-frozen samples will be collected for Exome Sequencing and RNA Sequencing. In the third year, validation of the gene amplifications and somatic mutation as well as protein markers using an additional validation set of samples from 500 FFPE samples and the above mentioned seven patients. We anticipate the elucidation of the mechanism of cancer progression from endometrial hyperplasia will aid in the finding of prevention and therapeutic targets.

Project ID:PC10107-0351
External Project ID:NSC101-2314-B182-046-MY3