Ovarian Cancer Coverage from Every Angle

Proteomic Analysis Identifies ADNP Gene as Mediator of Cell Proliferation in Ovarian Cancer

By: Kelly M. Hennessey, PhD
Posted: Tuesday, January 7, 2020

Investigators of a new study identified the activity dependent neuroprotector homeobox (ADNP) gene as a regulator of high-grade serous ovarian cancer, based on the association between poor prognosis and expression of the gene/protein. Michael L. Gatza, PhD, of Rutgers Cancer Institute, New Jersey, and colleagues confirmed the essentiality of the ADNP protein in mediating cell growth and survival by interrupting cell-cycle checkpoints in this type of ovarian cancer. Their results were published in EBioMedicine.

The overall prognosis for patients with high-grade serous ovarian cancer has not improved over the past several decades, underscoring the need to understand the mechanisms leading to tumor development and progression, the authors noted. To identify genes and mutations that contribute to ovarian cancer development, the researchers first examined patterns of oncogenic signaling. They found that high-grade serous ovarian tumors were largely homogenous; no subtype-specific patterns of oncogenic pathway activity were observed. Using an integrated proteogenomic strategy, they identified DNA alterations, altered mRNA expression, and protein expression associated with a poor prognosis gene-expression signature.

In vitro experiments confirmed the role of ADNP in ovarian cancer proliferation. The investigators found that this gene is essential for cell proliferation and survival and that ADNP silencing induces cell-cycle arrest. Collectively, their proteogenomic data and in vitro experiments identified this gene as a modulator in ovarian cancer tumorigenesis.

“How ADNP abrogates this process remains unclear,” commented the researchers. “As such, defining these mechanisms will be paramount for determining the therapeutic and/or biomarker potential of ADNP in high-grade serous ovarian cancer as well as other tumor types.”

Disclosure: The study authors reported no conflicts of interest.

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