Differential Mutation Frequencies in Metastatic Cutaneous Squamous Cell Carcinomas Versus Primary Tumors

    loading  Checking for direct PDF access through Ovid



Exome and targeted sequencing studies have identified potential driver mutations for a variety of tumor types. Cutaneous squamous cell carcinoma (cSCC) is one of the most highly mutated cancers but typically is associated with low rates of metastasis and high survival rates. Nevertheless, metastatic cSCC is a significant health threat; up to 8800 individuals die each year of this disease.


Because it is difficult to predict which cSCCs are more likely to metastasize, and because to the best of the authors' knowledge there are no targeted therapies specifically designated for patients with metastatic cSCC, exome and/or targeted sequencing of 18 metastatic and 10 primary cSCCs was performed to identify mutations that were more frequent in metastatic tumors and might be targeted for therapeutic benefit. The authors compared their results with published sequencing results of an additional 223 primary tumors and 68 metastatic cSCCs.


The authors identified genes demonstrating higher mutation frequencies in metastatic cSCC compared with primary tumors, including the chromatin remodeling gene lysine methyltransferase 2D (KMT2D) and the classic skin tumor suppressor tumor protein p53 (TP53), which was found to be mutated in 54% of primary tumors compared with 85% of metastatic tumors (P<.0001).


These studies appear to uncover potential pathways that are important in metastatic cSCC and that broaden understanding of the biology contributing to aggressive tumor behavior. These results may lead to new therapeutic strategies.

Exome and/or targeted deep sequencing analysis of 10 primary cutaneous squamous cell carcinoma (cSCC) and 18 metastatic cSCC samples demonstrated mutations in known skin cancer-related genes such as TP53 and NOTCH1. Combining frequency data from primary and metastatic cSCCs from the current study with those in the literature demonstrated a higher mutation frequency in TP53 and KMT2D in metastatic tumors compared with nonmetastatic cSCC samples.

Related Topics

    loading  Loading Related Articles