MOCRC and Feel Teal are helping to better understand ovarian cancer

Monday 09 July 2018

Mater researcher Professor Geoff Faulkner’s team, in collaboration with gynaecological oncologists from Mater Health, Mater Pathology, the Feel Teal initiative and the Mater Ovarian Cancer Research Collaboration (MOCRC) are making strides towards a better understanding of ovarian cancer.

Ovarian cancer is the eighth most prevalent cancer affecting women in Australia*. High-grade serous ovarian carcinoma (HGSOC) is the most common type of ovarian tumour and causes an estimated 125 000 deaths a year worldwide. Acquired resistance to chemotherapy is a major driver of HGSOC patient mortality.

In collaboration with MOCRC, and Mater Health, Professor Faulkner and his lab conducted a genomic analysis of 19 ovarian cancer patients from Mater. They analysed LINE-1 mobile DNA activity in HGSOC samples. Their research revealed that mobile DNA activity, and the diverse character of ovarian tumours, has the potential to impact treatment and patient outcomes. 

Chemoresistance occurs when some of the cells in a tumour treated with chemotherapy are not killed by the drug, and then mutate to become resistant to future treatments. Once those cells multiply again, the tumour is mainly comprised of cells that are resistant to chemotherapy. New “genomic” tools can allow researchers to identify mutations associated with chemoresistance.

“Genomic analysis of tumours is becoming increasingly routine in deciding upon the best treatment for a given type of cancer.” Professor Faulkner said.

They showed how a LINE-1 mutation in one patient tumour, inserted in the chemoresistance gene STC1, allowed STC1 to become more active. Once the tumour was treated with chemotherapy, the LINE-1 mutation expanded greatly to essentially take over the tumour and make nearly all of its cells chemoresistant. This is an important example of how LINE-1 mutations can be selected for, i.e. increase in prevalence, during chemotherapy. 

“This work should be useful because it shows how LINE-1 mutations, which can be discovered by genomic analysis, can impact how a tumour responds to chemotherapy. Having this information could potentially change clinical management.”

“The study was only possible due to the successful collaboration with Prof Lew Perrin and other Mater Gynaecological Oncology Service clinicians, as well as the generosity of their patients, who provided samples for research.”

 

Publication: 

Nguyen, T.H.M., Carreira, P.E., Sanchez-Luque, F.J., Schauer, S.N., Fagg, A.C., Richardson, S.R., Davies, C.M., Jesuadian, J.S., Kempen, M-J.H.C., Troskie, R-L., James, C., Beaven, E.A., Wallis, T.P., Coward, J.I.G., Chetty, N.P., Crandon, A.J., Venter, D.J., Armes, J.E., Perrin, L.C., Hooper, J.D., Ewing, A.D., Upton, K.R., Faulkner, G.J. L1 retrotransposon heterogeneity in ovarian tumor cell evolution. Cell Reports 23 1-11 (2018)

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