SNU research team unveils the evolutionary process of tumor related to ovarian cancer metastasis

It has been observed that metastatic tumors of ovarian cancer, which has the highest mortality and recurrence rate among women’s cancer, is due to a different genetic mutation from the primary tumors.

It was announced on the 11th that the SNU team of Prof. Yong Sang Song(Seoul National University Hospital, Obstetrics & Gynecology) and Prof. Sunghoon Kwon(Dept. of Electrical and Computer Engineering) analyzed genomes and constructed phylogenetic trees that visualize evolution in the shape of branches in order to investigate the genetic evolution of ovarian cancer cells.

The research team constructed phylogenetic trees by taking 17 tumor tissue samples from left and right ovaries as well as malignant ascites. As a result, metastatic tumor cells found in the ascites were classified to be of a different lineage from the primary tumor cells.

The research team utilized laser-aided cell isolation technique, a next-generation diagnosis technology, in order to separate tumor samples from a patient diagnosed with grade 3 ovarian cancer. Primary tumor samples were collected from 7 locations in the right ovary and 1 in the left ovary, and 10 tissue samples were separated from tumor spheroids within the malignant ascites. Afterwards, whole-genome sequencing and whole-exome sequencing were performed on each of the ovarian cancer cells for comparison with normal tissues. As a result of this research, a total of 171 single-nucleotide variants(SNVs) were identified. 38.6% of these SNVs were found in both primary and metastatic tumors, 35.7% were unique to primary tumors, and 25.7% were found exclusively in metastasized regions. In other words, the ratio of SNVs that are common to both primary tumor sites and metastasized regions was low. This implies that the metastasized region may have diverged from the primary tumor in the early stages of ovarian cancer development and accumulated genetic mutations independently.

This means that ovarian cancer clones formed in the early stages are metastasized to ascites and create tumor spheroids, but not all primary region clones form cancer cells in metastasized regions and the metastasized tumors accumulate mutations independently.

Unlike other cancer patients, most epithelial ovarian cancer(EOC) patients experience ascites and metastasis to the serous fluid. Professor Song commented on the significance of the research, saying, “Because there are neither unusual symptoms nor effective diagnosis methods for ovarian cancer, in many cases, the cancer has already spread by the time of diagnosis. This research has provided the foundation for research on predicting the evolutionary direction of tumors related to ovarian cancer metastasis.”

This research was supported by National Research Foundation with fundings from Ministry of Science and ICT, and was published in a recent issue of the international journal ‘Scientific Reports’. Furthermore, as a move to promote global research and development centers(GRDC), Ph.D. candidate Sungsik Kim of SNU, Ph.D. Soochi Kim of Stanford University, and Se Ik Kim of Seoul National University Hospital Dept. of Obstetrics and Gynecology participated as co-researchers.

Source: http://ee.snu.ac.kr/community/news?bm=v&bbsidx=47922
Translated by: Jee Hyun Lee, English Editor of Department of Electrical and Computer Engineering, jlee621@snu.ac.kr