Nf2/Merlin controls spinal cord neural progenitor function in a Rac1/ErbB2-dependent manner

Objective: Individuals with the neurofibromatosis type 2 (NF2) cancer predisposition syndrome develop spinal cord glial tumors (ependymomas) that likely originate from neural progenitor cells. Whereas many spinal ependymomas exhibit indolent behavior, the only treatment option for clinically symptomatic tumors is surgery. In this regard, medical therapies are unfortunately lacking due to an incomplete understanding of the critical growth control pathways that govern the function of spinal cord (SC) neural progenitor cells (NPCs). Methods: To identify potential therapeutic targets for these tumors, we leveraged primary mouse Nf2-deficient spinal cord neural progenitor cells. Results: We demonstrate that the Nf2 protein, merlin, negatively regulates spinal neural progenitor cell survival and glial differentiation in an ErbB2-dependent manner, and that NF2-associated spinal ependymomas exhibit increased ErbB2 activation. Moreover, we show that Nf2-deficient SC NPC ErbB2 activation results from Rac1-mediated ErbB2 retention at the plasma membrane. Significance: Collectively, these findings establish ErbB2 as a potential rational therapeutic target for NF2-associated spinal ependymoma

Gastric Pouch Mixed Adenoneuroendocrine Carcinoma With a Mixed Adenocarcinoma Component After Roux-en-Y Gastric Bypass

The Roux-en-Y gastric bypass is one of the most common procedures currently performed for surgical treatment of patients with severe obesity. Gastric cancer after bariatric surgery is not common, with most of them arising in the excluded stomach. Gastric mixed adenoneuroendocrine carcinomas are a rare type of stomach malignancy, composed of both adenocarcinoma and neuroendocrine tumor-cell components, with the latter comprising at least 30% of the whole neoplasm. In this article, we report a unique case of a mixed adenoneuroendocrine carcinoma with a mixed adenocarcinoma (tubular and poorly cohesive) component arising in the gastric pouch of a patient who underwent previous Roux-en-Y gastric bypass for glycemic control. Since stomach cancer is not usual in patients who have formerly undergone bariatric surgery and symptoms tend to be nonspecific, such diagnosis is often rendered at an advanced stage. Full assessment of these patients when presenting such vague symptoms is critical for an early cancer diagnosis