McPherson A, Roth A, Laks E, Masud T, Bashashati A, Zhang AW, Ha G, Biele J, Yap D, Wan A, Prentice L, Khattra J, Mullaly SC, Kalloger S, Karnezis A, Shumansky K, Siu C, Rosner J, Chan HL, Ho J, Melnyk N, Senz J, Yang W, Moore R, Mungall A, Marra MA, Bouchard-Cote A, Gilks CB, Huntsman DG, McAlpine J, Aparicio S, Shah SP. Divergent Modes of Clonal Spread and Intraperitoneal Mixing in High-Grade Serous Ovarian Cancer. Nature Genetics. Published online May 16, 2016.doi:10.1038/ng.3573
Our Nature Genetics paper tracked the patterns of metastatic spread in the peritoneal cavity of patients with high grade serous ovarian cancer. we identify at least two divergent modes of intraperitoneal metastasis, highlighting the interplay between genomically diverse clones and their migratory potential prior to therapeutic intervention in high grade serous ovarian cancers.
Vancouver – BC Cancer Agency researchers are providing critical insight into the invasive spread of the most malignant form of ovarian cancer in a landmark study, published today in Nature Genetics. This is a first in mapping two distinct patterns of ovarian cancer cell migration in high grade serous ovarian cancer.
The discovery, led by Dr. Sohrab Shah, senior scientist at the BC Cancer Agency, Associate Professor at the University of British Columbia, and Canada Research Chair in Computational Cancer Genomics, was made possible through genomic sequencing techniques and novel software developed by his bioinformatics team at the BC Cancer Agency. The study was simultaneously published today in Nature Methods. The scientists have answered key unknowns about how deadly ovarian cancers spread, and the composition of the cancer cell groups that have taken up residence within the patient’s abdomen.
The study reveals that many cancer cell types make up a patient’s tumour. This could explain why some cells are susceptible to treatment when others are resistant, leading to relapse. Also, cell type migration patterns from ovary to other abdominal sites identified that specific ovary sites contained many more cell types relative to others. These regions could pinpoint ‘gateways’ of cell migration to other abdominal sites.
More than 300 women are diagnosed with ovarian cancer each year in BC, and 80 per cent of women diagnosed with a high grade serous ovarian cancer relapse, despite an initial response to treatment. Unlike most cancers that spread through the blood stream or lymph system, this study shows that high grade serous ovarian cancer cells have a unique opportunity to spread prolifically throughout the abdomen. In mapping the cell migration, Dr. Shah’s team shows how cells are able to settle and thrive in specific regions of the body causing widespread, life-threatening disease.
The migration maps were primarily determined in pre-treatment samples with one exception. Shah’s team studied one patient with multiple relapse specimens. Notably, only a subset of cancer cells present at diagnosis led to treatment resistance.
Next steps are to use the innovative techniques developed for this study to define cell migration maps from additional patients over time with a specific focus on determining which cells are resistant to treatment. This will allow researchers to build predictive tools to better inform future care.
This new understanding of how high grade serous ovarian cancer cells migrate within the patient’s body provides insight that could inform future treatment selection. These results indicate that some cancer cells may have had pre-existing properties of resistance prior to the patient taking any treatment. This could indicate that a patient requires a much more aggressive, multi-treatment approach from the start to prevent relapse.
This work is supported by the BC Cancer Foundation through the generosity of donors from across BC who are committed to improving cancer outcomes for those impacted by ovarian cancer.
- More than 300 women are diagnosed with ovarian cancer each year in BC
- Approximately 250 women die from ovarian cancer each year in the province.
- High grade serous carcinoma is the most malignant form of ovarian cancer and accounts for up to 70 per cent of all ovarian cancer cases
- High grade serous ovarian cancers have been proven to originate in the fallopian tube, not the ovary
- 80 per cent of women diagnosed with a high grade serous ovarian cancer relapse despite an initial response to treatment.