GRCh37 · COSMIC v97


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Mutational Landscape of Ovarian Adult Granulosa Cell Tumors from Whole Exome and Targeted TERT Promoter Sequencing.
Paper ID
Alexiadis M, Rowley SM, Chu S, Leung DTH, Stewart CJR, Amarasinghe KC, Campbell IG and Fuller PJ
Centre for Endocrinology and Metabolism, Hudson Institute of Medical Research.
Molecular cancer research : MCR, 2018
ISSN: 1557-3125
PMID: 30166312 (view at PubMed or Europe PMC)
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 was 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 suggested an association with DNA replication/repair and the epidermal growth factor receptor (EGFR) family canonical pathways. Copy number analysis confirmed that gains of chromosomes 12 and 14 occur in ~30% of aGCT and loss of chromosome 22 occurs in ~40% of cases. In summary, exome-wide analysis of the mutational landscape of aGCT revealed that, except for the TERT promoter mutation, recurrence and/or aggressive behavior is not defined by activation or loss of specific genes.Implications: This study found that although aGCTs are defined by the presence of a common FOXL2 gene mutation, recurrence and/or aggressive behavior cannot be attributed to subsequent mutation of specific gene(s) or pathways; however, there is a high frequency of the TERT -124C>T promoter mutation which is associated with more aggressive disease.
Paper Status