Dr. Trombetta on Recurrent NRG1 Rearrangements in Invasive Mucinous Adenocarcinoma

Domenico Trombetta, PhD, researcher, laboratory of oncology, Fondazione IRCCS Casa Sollievo della Sofferenza, discusses findings from an Italian multicenter cohort of patients with invasive mucinous adenocarcinoma (IMA), a rare histotype of lung adenocarcinoma.

NRG1 rearrangement is a new subtype-specific molecular feature of IMA which serves as a strong oncogenic inductor of the aberrant tyrosine kinase activity of ErbB2/ErbB3 heterodimers through PI3K-AKT/MAPK cellular cascades.

For the first time, investigators were able to describe the occurrence of these arrangements in 32% of Caucasian patients with lung IMAs, says Trombetta, showing both NRG1 fluorescent in situ hybridization (FISH) split signals and deletions of the 5’ portion of the gene.

The use of immunohistochemistry confirmed previous findings regarding the link between pErbB3 immunoreactivity and NRG1 rearrangements, as well as the heterogeneity of fluorescent signal distribution and immunostaining along the tissue sections. Correlation analysis among clinical pathological data, pErbB3 expression, and NRG1 rearrangements are ongoing, adds Trombetta.

These findings, presented at the 2019 AACR Annual Meeting, also underscore the role of NRG1 rearrangement as a master molecular marker of lung IMAs, one that can potentially be used by physicians to select patients for emerging targeted therapies.