Genetic Mutations of Pancreatic Cancer and Genetically Engineered Mouse Models

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy, and the seventh leading cause of cancer-related deaths worldwide. An improved understanding of tumor biology and novel therapeutic discoveries are needed to improve overall survival. Recent multi-gene analysis approaches such...

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Published inCancers Vol. 14; no. 1; p. 71
Main Authors Saiki, Yuriko, Jiang, Can, Ohmuraya, Masaki, Furukawa, Toru
Format Journal Article
LanguageEnglish
Published Switzerland MDPI AG 24.12.2021
MDPI
Subjects
Adenocarcinoma
Animal models
Cell lineage
CRISPR
DNA damage
Genes
Genetic engineering
Genomes
Inflammation
Kinases
Lesions
Malignancy
Medical prognosis
Metastases
Mutation
Neoplasia
Next-generation sequencing
Pancreatic cancer
Pancreatitis
Phase transitions
Proteins
Recombinase
Review
Transcription factors
Tumorigenesis
Tumors
KRAS
PDAC
GEMM
Online AccessGet full text

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Abstract Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy, and the seventh leading cause of cancer-related deaths worldwide. An improved understanding of tumor biology and novel therapeutic discoveries are needed to improve overall survival. Recent multi-gene analysis approaches such as next-generation sequencing have provided useful information on the molecular characterization of pancreatic tumors. Different types of pancreatic cancer and precursor lesions are characterized by specific molecular alterations. Genetically engineered mouse models (GEMMs) of PDAC are useful to understand the roles of altered genes. Most GEMMs are driven by oncogenic Kras, and can recapitulate the histological and molecular hallmarks of human PDAC and comparable precursor lesions. Advanced GEMMs permit the temporally and spatially controlled manipulation of multiple target genes using a dual-recombinase system or CRISPR/Cas9 gene editing. GEMMs that express fluorescent proteins allow cell lineage tracing to follow tumor growth and metastasis to understand the contribution of different cell types in cancer progression. GEMMs are widely used for therapeutic optimization. In this review, we summarize the main molecular alterations found in pancreatic neoplasms, developed GEMMs, and the contribution of GEMMs to the current understanding of PDAC pathobiology. Furthermore, we attempted to modify the categorization of altered driver genes according to the most updated findings.
AbstractList Simple SummaryPancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy. Recent multi-gene analysis approaches such as next-generation sequencing have provided useful information on the molecular characterization of pancreatic tumors. Different types of pancreatic cancer and precursor lesions are characterized by specific molecular alterations. Genetically engineered mouse models (GEMMs) of PDAC are useful tools to understand the roles of altered genes. Most GEMMs are driven by oncogenic Kras, and can recapitulate the histological and molecular hallmarks of human PDAC and comparable precursor lesions. In this review, we summarize the main molecular alterations found in pancreatic neoplasms and GEMMs developed based on these alterations.AbstractPancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy, and the seventh leading cause of cancer-related deaths worldwide. An improved understanding of tumor biology and novel therapeutic discoveries are needed to improve overall survival. Recent multi-gene analysis approaches such as next-generation sequencing have provided useful information on the molecular characterization of pancreatic tumors. Different types of pancreatic cancer and precursor lesions are characterized by specific molecular alterations. Genetically engineered mouse models (GEMMs) of PDAC are useful to understand the roles of altered genes. Most GEMMs are driven by oncogenic Kras, and can recapitulate the histological and molecular hallmarks of human PDAC and comparable precursor lesions. Advanced GEMMs permit the temporally and spatially controlled manipulation of multiple target genes using a dual-recombinase system or CRISPR/Cas9 gene editing. GEMMs that express fluorescent proteins allow cell lineage tracing to follow tumor growth and metastasis to understand the contribution of different cell types in cancer progression. GEMMs are widely used for therapeutic optimization. In this review, we summarize the main molecular alterations found in pancreatic neoplasms, developed GEMMs, and the contribution of GEMMs to the current understanding of PDAC pathobiology. Furthermore, we attempted to modify the categorization of altered driver genes according to the most updated findings.
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy, and the seventh leading cause of cancer-related deaths worldwide. An improved understanding of tumor biology and novel therapeutic discoveries are needed to improve overall survival. Recent multi-gene analysis approaches such as next-generation sequencing have provided useful information on the molecular characterization of pancreatic tumors. Different types of pancreatic cancer and precursor lesions are characterized by specific molecular alterations. Genetically engineered mouse models (GEMMs) of PDAC are useful to understand the roles of altered genes. Most GEMMs are driven by oncogenic Kras, and can recapitulate the histological and molecular hallmarks of human PDAC and comparable precursor lesions. Advanced GEMMs permit the temporally and spatially controlled manipulation of multiple target genes using a dual-recombinase system or CRISPR/Cas9 gene editing. GEMMs that express fluorescent proteins allow cell lineage tracing to follow tumor growth and metastasis to understand the contribution of different cell types in cancer progression. GEMMs are widely used for therapeutic optimization. In this review, we summarize the main molecular alterations found in pancreatic neoplasms, developed GEMMs, and the contribution of GEMMs to the current understanding of PDAC pathobiology. Furthermore, we attempted to modify the categorization of altered driver genes according to the most updated findings.
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy, and the seventh leading cause of cancer-related deaths worldwide. An improved understanding of tumor biology and novel therapeutic discoveries are needed to improve overall survival. Recent multi-gene analysis approaches such as next-generation sequencing have provided useful information on the molecular characterization of pancreatic tumors. Different types of pancreatic cancer and precursor lesions are characterized by specific molecular alterations. Genetically engineered mouse models (GEMMs) of PDAC are useful to understand the roles of altered genes. Most GEMMs are driven by oncogenic Kras, and can recapitulate the histological and molecular hallmarks of human PDAC and comparable precursor lesions. Advanced GEMMs permit the temporally and spatially controlled manipulation of multiple target genes using a dual-recombinase system or CRISPR/Cas9 gene editing. GEMMs that express fluorescent proteins allow cell lineage tracing to follow tumor growth and metastasis to understand the contribution of different cell types in cancer progression. GEMMs are widely used for therapeutic optimization. In this review, we summarize the main molecular alterations found in pancreatic neoplasms, developed GEMMs, and the contribution of GEMMs to the current understanding of PDAC pathobiology. Furthermore, we attempted to modify the categorization of altered driver genes according to the most updated findings.Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy, and the seventh leading cause of cancer-related deaths worldwide. An improved understanding of tumor biology and novel therapeutic discoveries are needed to improve overall survival. Recent multi-gene analysis approaches such as next-generation sequencing have provided useful information on the molecular characterization of pancreatic tumors. Different types of pancreatic cancer and precursor lesions are characterized by specific molecular alterations. Genetically engineered mouse models (GEMMs) of PDAC are useful to understand the roles of altered genes. Most GEMMs are driven by oncogenic Kras, and can recapitulate the histological and molecular hallmarks of human PDAC and comparable precursor lesions. Advanced GEMMs permit the temporally and spatially controlled manipulation of multiple target genes using a dual-recombinase system or CRISPR/Cas9 gene editing. GEMMs that express fluorescent proteins allow cell lineage tracing to follow tumor growth and metastasis to understand the contribution of different cell types in cancer progression. GEMMs are widely used for therapeutic optimization. In this review, we summarize the main molecular alterations found in pancreatic neoplasms, developed GEMMs, and the contribution of GEMMs to the current understanding of PDAC pathobiology. Furthermore, we attempted to modify the categorization of altered driver genes according to the most updated findings.
Author Ohmuraya, Masaki
Saiki, Yuriko
Jiang, Can
Furukawa, Toru
AuthorAffiliation 2 Department of Genetics, Hyogo College of Medicine, Hyogo 663-8501, Japan; ohmuraya@hyo-med.ac.jp
1 Department of Investigative Pathology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan; ysaiki@med.tohoku.ac.jp (Y.S.); can.jiang.t3@dc.tohoku.ac.jp (C.J.)
AuthorAffiliation_xml – name: 1 Department of Investigative Pathology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan; ysaiki@med.tohoku.ac.jp (Y.S.); can.jiang.t3@dc.tohoku.ac.jp (C.J.)
– name: 2 Department of Genetics, Hyogo College of Medicine, Hyogo 663-8501, Japan; ohmuraya@hyo-med.ac.jp
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  surname: Saiki
  fullname: Saiki, Yuriko
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  orcidid: 0000-0002-1083-2324
  surname: Furukawa
  fullname: Furukawa, Toru
BackLink https://www.ncbi.nlm.nih.gov/pubmed/35008235$$D View this record in MEDLINE/PubMed
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Snippet Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy, and the seventh leading cause of cancer-related deaths worldwide. An improved...
Simple SummaryPancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy. Recent multi-gene analysis approaches such as next-generation...
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StartPage 71
SubjectTerms Adenocarcinoma
Animal models
Cell lineage
CRISPR
DNA damage
Genes
Genetic engineering
Genomes
Inflammation
Kinases
Lesions
Malignancy
Medical prognosis
Metastases
Mutation
Neoplasia
Next-generation sequencing
Pancreatic cancer
Pancreatitis
Phase transitions
Proteins
Recombinase
Review
Transcription factors
Tumorigenesis
Tumors
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Title Genetic Mutations of Pancreatic Cancer and Genetically Engineered Mouse Models
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Volume 14
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