Metastatic penile carcinoma associated with convergent gain-of-function mutations in NOTCH1

Publication date: March 2018 Source:Human Pathology: Case Reports, Volume 11 Author(s): Sabina Signoretti, Jon C. Aster Notch receptors (NOTCH1-4) participate in a signaling pathway that is frequently dysregulated in cancer and that has different consequences depending on cell lineage, allowing it to have oncogenic or tumor suppressive effects. One well-characterized context in which Notch is tumor suppressive is squamous cell carcinoma, as after mutations in TP53, mutations that disrupt Notch receptor activity are the most common mutations in cutaneous squamous cell carcinoma. However, Notch signaling also can be oncogenic in other types of epithelial neoplasms. Here, we report a unique case of metastatic penile squamous cell carcinoma associated with high levels of activated NOTCH1 and two different NOTCH1 gain-of-function mutations. This case emphasizes the remarkable variability of Notch effects in cancers, even within tumors of the same lineage, and suggests that in rare instances Notch may be a valid therapeutic target in squamous cancers.
Source: Human Pathology: Case Reports - Category: Pathology Source Type: research