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.

... 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

... 0 1 3 SOD2 0 0 2 SULT1A2 0 1 2 ZNF142 0 0 2 In addition, we also found nine genes (C7orf70, DNHD1, KPRP, MDM4, MUC6, OR51Q1, PTPRD, TCF4, and TET2) that possess no mutation in ACs. Among these nine mutated genes, four genes (DNHD1, OR51Q1, PTPRD, and TCF4) were discovered to possess SNVs exclusively in SCCs (Table 5 ). The analysis of Gene Ontology (GO) discovered that these nine mutated genes were involved in the following main biological processes: histone H3K4 methylation (GO:0051568), DNA methylation (GO: 0080111) and negative regulation of cell cycle arrest (GO: 0071157) (Figure 2E ). For the GO category of molecular functions, these nine mutated genes were mainly involved in basal transcription machinery binding (GO: 0001098), ferrous iron binding (GO:0008198) and LRR domain binding (GO: 0030275) (Figure 2F ). Table 5 Summary of specific mutated genes in pancreatic SCC and ASC tissues Gene Squamous Cell Carcinoma (SCC) Adenosquamous Carcinoma (ASC) Adenocarcinoma (AC) C7orf70 2 1 0 DNHD1

..., is supposed to be associated with bladder cancer and breast cancer [ 58 , 59 ]. ZNF142 is related to transcriptional regulation, controlling cell growth, proliferation, differentiation, and apoptosis. We also detected nine mutated genes (C7orf70, DNHD1, KPRP, MDM4, MUC6, OR51Q1, PTPRD, TCF4, TET2) in SCCs or ASCs (Table 5 ), among which four genes (DNHD1, OR51Q1, PTPRD, TCF4) were mutated only in SCCs (Highlighted in red in Table 5 ). DNHD1 and OR51Q1 are known very little, but a clinical genomics study shows that DNHD1 is harbored independent homozygous mutations in patients with overlapping phenotypes [ 60 ]. PTPRD is known to regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. Studies also identified deletion of PTPRD in head and neck SCC [ 61 ]. TCF4 encodes transcription factor 4, and is closely related to the canonical Wnt pathway, which plays key roles in development, tissue homeostasis, and cancer

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Gene: DNHD1 - dynein heavy chain domain 1 - (NCBI)

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