Journal article

Mutational Landscape of Ovarian Adult Granulosa Cell Tumors from Whole Exome and Targeted TERT Promoter Sequencing

Maria Alexiadis, Simone M Rowley, Simon Chu, Dilys TH Leung, Colin JR Stewart, Kaushalya C Amarasinghe, Ian G Campbell, Peter J Fuller



Adult granulosa cell tumor (aGCT), the most common malignant ovarian sex cord-stromal tumor, is characterized by the forkhead transcription factor FOXL2 p.C134W somatic mutation. Late recurrences are relatively common but the molecular mechanisms of relapse or aggressive behavior are not known. The mutational landscape of FOXL2 p.C134W mutation-positive tumors (n = 22) was determined using whole-exome sequencing (WES). An average of 64 coding and essential splice-site variants were identified per tumor. As the TERT promoter region is poorly covered by the WES, targeted sequencing identified the TERT -124C>T promoter mutation as the only recurrent mutation (∼40% of cases). Pathway analysis su..

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Awarded by National Health & Medical Research Council of Australia

Funding Acknowledgements

The authors wish to thank Nicole Fairweather, Prof. Martin Oehler and Zdenka Prodanovic (Victorian Cancer Biobank) for assistance with collection of the tissue samples and clinical information; Trevor Wilson for advice on the WES; Haroon Naeem from Monash Bioinformatics Platform for assisting us with the pathway analysis using Ingenuity Pathway Analysis (IPA) tool and Sue Panckridge for preparation of the figures. This work is supported by grants from the Cancer Council Victoria; the Ovarian Cancer Research Foundation (to S. Chu); the Granulosa Cell Tumor of the Ovary Foundation; the National Health & Medical Research Council of Australia through a project grant (#1058334) and a Senior Principal Research Fellowship (to P.J. Fuller; #1002559); and the Endocrine Society of Australia through a Research Higher Degree Scholarship (to D.T.H. Leung). The Hudson Institute and the Peter McCallum Cancer Centre are supported by the Victorian Government's Operational Infrastructure Scheme.