Genomic characteristics of pancreatic squamous cell carcinoma, an investigation by using high throughput sequencing after in-solution hybrid capture

Abstract

Squamous cell carcinoma (SCC) of pancreas is a rare histotype of pancreatic ductal carcinoma which is distinct from pancreatic adenocarcinoma (AC). Although there are standard treatments for pancreatic AC, no precise therapies exist for pancreatic SCC. Here, we screened 1033 cases of pancreatic cancer and identified 2 cases of pure SCC, which were pathologically diagnosed on the basis of finding definite intercellular bridges and/or focal keratin peal formation in the tumor cells. Immunohistochemistry assay confirmed the positive expression of CK5/6 and p63 in pancreatic SCC. To verify the genomic characteristics of pancreatic SCC, we employed in-solution hybrid capture targeting 137 cancer-related genes accompanied by high throughput sequencing (HTS) to compare the different genetic variants in SCC and AC of pancreas. We compared the genetic alterations of known biomarkers of pancreatic adenocarcinoma in different pancreatic cancer tissues, and identified nine mutated genes in SCC of pancreas: C7orf70, DNHD1, KPRP, MDM4, MUC6, OR51Q1, PTPRD, TCF4, TET2, and nine genes (ABCB1, CSF1R, CYP2C18, FBXW7, ITPA, KIAA0748, SOD2, SULT1A2, ZNF142) that are mutated in pancreatic AC. This study may have taken one step forward on the discovery of potential biomarkers for the targeted treatment of SCC of the pancreas.

PTPRD: neurobiology, genetics, and initial pharmacology of a pleiotropic contributor to brain phenotypes

“…There are reported associations between PTPRD variation and a number of cancers or their responses to treatment . While the details of these associations are beyond the scope of this paper, we note that most come from genotyping tumors or tumor‐derived cell lines and that none of these associations focuses on the mid‐gene regions that we have associated with a number of brain phenotypes and levels of PTPRD expression.…”

Hybrid Capture-Based Next Generation Sequencing and Its Application to Human Infectious Diseases

“…Following this, many targeted human exome in-solution enrichment methods for NGS have been developed, including those commercialized by Illumina 1 and Agilent Genomics 2 ( Chen et al, 2015a , b ). In-solution capture for exome sequencing turned out to be an effective approach applied to discover the causal mutation of rare Mendelian disorders ( Shearer et al, 2010 ; Martignetti et al, 2013 ; Nectoux et al, 2015 ; Rousseau-Nepton et al, 2015 ), of complex disorders ( Poultney et al, 2013 ; Guipponi et al, 2014 ; Griesi-Oliveira et al, 2015 ; Pérez-Serra et al, 2015 ), mitochondrial disorders ( Calvo et al, 2012 ; Gai et al, 2013 ) and more recently of the screening of potential genetic mutation of patients suffering from cancer ( Sikkema-Raddatz et al, 2013 ; Drilon et al, 2015 ; Xie et al, 2016 ; Rozenblum et al, 2017 ; Xu et al, 2017 ; Clark T.A. et al, 2018 ; Schrock et al, 2018 ).…”

Neutrophil/lymphocyte ratio is a more sensitive systemic inflammatory response biomarker than platelet/lymphocyte ratio in the prognosis evaluation of unresectable pancreatic cancer

“…Even for those who received surgery, they might finally suffer from recurrence or metastasis. Chemotherapy is still one of the major treatments for pancreatic cancer [ 1 ] [ 2 ] [ 3 ].…”