Research Highlight March 31, 2016

Progression mechanisms in associated benign and invasive ovarian tumors

Brenner tumors are rare, mostly benign ovarian growths. Although they are non-malignant themselves, they frequently co-occur with mucinous neoplasms, which may be invasive and are difficult to interpret with current pathology techniques. Little molecular characterization has been conducted with Brenner tumors and co-occurring mucinous neoplasms, however, to determine if they share an origin and progression mechanisms.

A team of researchers from Dartmouth and JAX, led by Susan Mockus, Ph.D., manager of clinical analytics and curation at JAX, used the JAX Cancer Treatment Profile (CTP) assay to analyze eight benign ovarian Brenner tumors, six associated mucinous neoplasms and two atypical proliferative (borderline) Brenner tumors from patients. The CTP is a panel that detects single-nucleotide variants and copy number variants in 358 known or implicated cancer genes. What the authors found, reported in the March issue of The American Journal of Pathology, indicates a shared origin and provides a model for progression from a benign Brenner tumor to a potentially malignant mucinous neoplasm.

The Brenner tumors likely derive from altered fallopian tube epithelium cells that seed the ovary. As these cells divide, they may accumulate other genetic alterations. The researchers found two primary drivers—both known oncogenes—in the mucinous neoplasms that were not found in the associated Brenner tumors. One is associated with a RAS mutation combined with disruption of p16, an important negative/inhibitory regulator. The other is MYC and CDK4/CNND1 amplification that had not been previously reported. It appears to be an either/or mechanism, as changes to RAS and MYC were not found to co-occur. The finding may point to divergent traits and progression of these neoplasms and more precise molecular characterization.

Tafe et al., 2016. Molecular Genetic Analysis of Ovarian Brenner Tumors and Associated Mucinous Epilthelial Neoplasms. The American Journal of Pathology, 186:671-677