Format

Send to

Choose Destination
Pancreatology. 2018 Apr;18(3):318-327. doi: 10.1016/j.pan.2018.01.006. Epub 2018 Jan 31.

High throughput gene sequencing reveals altered landscape in DNA damage responses and chromatin remodeling in sporadic pancreatic neuroendocrine tumors.

Author information

1
Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China.
2
Genenexus Technology Corporation, 200433, China.
3
Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China. Electronic address: longjiang@fudanpci.org.
4
Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China. Electronic address: yuxianjun@fudanpci.org.

Abstract

PURPOSE:

The main objectives of this retrospective study were to survey the genetic landscape of PNETs in a clinical cohort by using the high throughput gene sequencing method and to determine cellular signaling networks affected by the uncovered gene mutations.

MATERIALS AND METHODS:

We retrieved the demographics and tumor characteristics of 13 patients. Cellular DNA was extracted from fresh snap frozen tumor tissues and was subject to high throughput gene sequencing analysis using the Illumina NextSeq500 System. Furthermore, the interaction network was constructed from the input gene set by Reactome and performed gene set enrichment analysis was performed with a cutoff FDR of ≤0.01.

RESULTS:

Totally 74 mutated genes and 93 mutations were identified. The median number of mutations was 7 (range 1-20) and that of mutated genes was 6 (range 1-17). Among these mutations, 48 (51.6%) were substitution mutations, nine (9.7%) were duplication mutations, 28 (30.1%) were deletion mutations and eight (8.6%) were deletion/insertion mutations. Gene set enrichment analysis generated a network of 21 interactions, 10 of which were associated with DNA repair like the Fanconi anemia pathway, nucleotide excision repair, and homologous recombination repair, or chromosome maintenance. Moreover, 9 patients had one or more mutations in DNA repair genes including the mismatch repair genes MSH2/MSH6.

CONCLUSIONS:

The study has uncovered genetic alterations of genes implicated in DNA damage responses and chromatin remodeling. Our findings will prompt further studies into the role of these mutated genes in the oncogenesis and molecular stratification of PNETs.

KEYWORDS:

Genetic; Neuroendocrine tumor; Pancreas; Pathway; Sequencing

PMID:
29395620
DOI:
10.1016/j.pan.2018.01.006
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center