Title- Genomic landscape of squamous cell carcinoma- Different genetic pathways culminating in a common phenotype.

INTRODUCTION: Squamous cell carcinomas (SqCCs) are the most common solid tumors in humans and are found across multiple organ systems. Although, integrated analysis of genetic alterations divulge similarities between SqCCs from various body sites, certain genes appear to be more frequently mutated in a given SqCC. These subtle differences may hold the key to determining the differentiation characteristics and predicting aggressiveness of tumors. MATERIALS AND METHOD: Fifty-four cases of SqCCs, in which the primary location of the tumor could be ascertained by clinical and radiological findings, were included in this study. Next generation sequencing data was analyzed for recurrent genetic abnormalities. RESULTS: Genetic alterations were found in 219 genes in the 54 cases studied. TP53 mutations were found to be more frequent in pulmonary SqCCs (86.5%) as compared to non-pulmonary SqCCs (58.8%) (p<0.05). NOTCH gene family mutations and CREBBP mutations were limited to non-pulmonary SqCC (p<0.005) and were mutated in 41.2% and 17.6% cases. CONCLUSION: A detailed comparative analysis of the genetic alterations identified by sequencing identified higher frequency of TP53 mutations in lung SqCCs as compared to non-pulmonary SqCCs. NOTCH and CREBPP mutations were found to be absent in lung and head and neck SqCCs and more frequent in SqCCs from other locations.

The Roles of Matrix Metalloproteinases in Pancreatic Cancer.

Matrix metalloproteinases (MMPs) have long been implicated for roles in cancer initiation, tumor growth, and metastasis. However, pancreatic cancer clinical trials using broad-based MMP inhibitors were discouraging. To better evaluate the use of MMP inhibitors in pancreatic cancer, (a) more precise roles of individual MMPs in pancreatic cancer needed to be determined and (b) animal models that more accurately represented human pancreatic cancer needed to be developed. The last decade has seen substantial progress in both areas. MT1-MMP has been recognized as a critical mediator of several steps in pancreatic cancer progression, while MMP-9 appears to be an antitarget when considering pancreatic cancer therapies.