Technologies

Ovarian cancer is the 5th leading cause of cancer death in woman with approximately 70% of deaths is due to the high-grade serous carcinoma (HG-SC) subtype, which is typically detected at advanced stages due to lack of early screening tools. HG-SC is characterized by a high degree of heterogeneity among tumors and massive genome rearrangements, and recurrent mutations that are specific only to HG-SC have been difficult to identify, presumably due to the high heterogeneity among tumors. Dr. Laising Yen and his team identified CDKN2D-WDFY2 as a cancer-specific and inter-chromosomal fusion gene presented in 20% of HG-SC tumors, and this fusion gene has three key features:
1) It is by far the most frequent gene recombinant event found in this highly heterogeneous disease;
2) It is not present in the non-cancerous ovaries or fallopian tubes;
3) The exact same RNA junction is observed in the fusion transcript across patient samples, suggesting that this mutation leads to a specific aberrant protein function.
In a follow-up study, the researchers identified another HG-SC cancer-specific fusion gene, BCAM-AKT2, which leads to the translation of a constitutively activated AKT2 fusion kinase. The BCAM-AKT2 fusion is present in 7% of HG-SC samples studied, still a significant frequency considering the highly heterogeneous nature of this malignancy.

Publications

- CDKN2D-WDFY2 Is a Cancer-Specific Fusion Gene Recurrent in High-Grade Serous Ovarian Carcinoma. Kannan K, Coarfa C, Rajapakshe K, Hawkins SM, Matzuk MM, Milosavljevic , Yen L. PLoS Genet. 2014 Mar 27;10(3):e1004216. - Recurrent BCAM-AKT2 fusion gene leads to a constitutively activated AKT2 fusion kinase in high-grade serous ovarian carcinoma. Kannan K, Coarfa C, Chao PW, Luo L, Wang Y, Brinegar AE, Hawkins SM, Milosavljevic A, Matzuk MM, Yen L. Proc Natl Acad Sci U S A. 2015 Mar 2. [Epub]