CDKN2D-WDFY2 is a cancer-specific fusion gene recurrent in high-grade serous ovarian carcinoma

Kalpana Kannan ¹, Cristian Coarfa ², Kimal Rajapakshe ²

⁰Department of Pathology & Immunology, Baylor College of Medicine, Houston, Texas, United States of America; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, United States of America.

Plos Genetics +

|

March 29, 2014

View abstract on PubMed

Summary

Researchers discovered a new ovarian cancer fusion gene, CDKN2D-WDFY2, in 20% of high-grade serous ovarian cancers. This finding may help classify this heterogeneous cancer and offers a potential molecular signature for diagnosis.

Area Of Science

Oncology
Molecular Biology
Genetics

Background

Ovarian cancer, particularly the high-grade serous subtype, is a leading cause of cancer death in women.
Early detection is challenging as it's often diagnosed after metastasis.
High-grade serous ovarian cancer exhibits significant heterogeneity and genomic instability, complicating characterization.

Purpose Of The Study

To identify specific, recurrent recombinant events in high-grade serous ovarian cancer.
To characterize a novel fusion gene and its potential role in oncogenesis.
To explore the fusion gene as a molecular signature for sub-typing ovarian cancer.

Main Methods

High-throughput transcriptome sequencing of patient samples.
Experimental validation at DNA, RNA, and protein levels.
Genomic breakpoint identification and fusion construct transfection.

Main Results

A novel, cancer-specific inter-chromosomal fusion gene, CDKN2D-WDFY2, was identified in 20% of high-grade serous ovarian cancer samples.
The fusion gene was absent in non-cancerous ovarian and fallopian tube tissues.
Transfection studies revealed altered protein expression and modulation of the PI3K/AKT pathway.

Conclusions

The CDKN2D-WDFY2 fusion represents the most frequent recombinant event identified in high-grade serous ovarian cancer to date.
This fusion gene may indicate a major cellular lineage within this heterogeneous cancer.
CDKN2D-WDFY2 could serve as a crucial molecular signature for understanding and classifying high-grade serous ovarian carcinomas.

Related Concept Videos