Recurrent genetic alterations and biomarker expression in primary and metastatic squamous cell carcinomas of the vulva

Genes, pathways and vulvar carcinoma - New insights from next-generation sequencing studies

“…In the study of Han et al [28], who applied exome sequencing, mutations were detected in as many as 66 genes. NGS panels for specific genes (whole or fragments thereof) covering up to 143 genes were used in the other four analyzed studies [10,26,27,29]. Interestingly, Nooij et al [27] developed a customized a panel for the genes that were previously detected in VSCC and its precursors, as well as in head and neck squamous cell carcinoma which shares numerous biological features with VSCC.…”

“…Due to pleiotropic effects of NOTCH pathway activation in different cellular contexts, in the transformed cells Notch receptors may function as cell autonomous oncoproteins, cell autonomous tumor suppressors, or microenvironment-dependent oncoproteins [53]. In VSCC, at least half of the detected NOTCH1 mutations are predicted to be inactivating [27,29] which, in vulvar carcinogenesis, may suggest a tumor suppressor function of NOTCH1. Despite the pleiotropic effects of Notch signaling pathway, clinical studies applying diverse strategies to inhibit the Notch signaling pathway are being conducted [54].…”

Molecular Landscape of Vulvar Squamous Cell Carcinoma

“…Eight series (57%) were based exclusively on VSCC, whereas six (43%) included both VSCC and premalignant lesions. One study evaluated the molecular profiles in primary and metastatic VSCC in a subset of cases [29]. Eight studies (57%) analyzed only somatic mutations [25,28,[30][31][32][33][34][35], two studies (14%) focused only on copy number alterations [36,37], and four (28%) included both somatic mutation profiling and analysis of copy number alterations [27,29,38,39].…”

“…Three series [28,33,38] have identified statistical differences in TP53 alterations depending on the HPV status and four [25,29,31,39] have shown a tendency in TP53 enrichment in HPV-independent VSCC, often combined with CDKN2A alterations. Two studies, both conducted by the same group [30,34], have not shown any differences for TP53 or CDKN2A mutations based on HPV status.…”

“…In most of the included studies, the authors suggested therapeutic molecular targets based on the molecular alterations identified. Targeting the PI3K/AKT/mTOR pathway was the most frequently proposed strategy among the reviewed series [27][28][29][30][31][33][34][35]. Williams et al [33] suggested that patients with KMT2D mutations might benefit from aurora kinase inhibitors.…”