Molecular Evidence for Monoclonal Skip Progression in Main Duct Intraductal Papillary Mucinous Neoplasms of the Pancreas

Kenjiro Date, Ohtsuka Takao, Takaaki Fujimoto, Koji Tamura, Hideyo Kimura, Taketo Matsunaga, Naoki Mochidome, Tetsuyuki Miyazaki, Yasuhisa Mori, Yoshinao Oda, Masafumi Nakamura, Masao Tanaka

研究成果: ジャーナルへの寄稿記事

5 引用 (Scopus)

抄録

Objective: To clarify clonality of distinct multisegmental main duct (MD)-intraductal papillary mucinous neoplasms (IPMNs) using microarray analysis. Background: IPMNs represent a pancreatic ductal cell field defect, which causes multiple occurrences of lesions. In addtion, it has been speculated that MD-IPMNs display features of monoclonal skip progression. Methods: Total RNA was extracted from fresh-frozen tissue samples of metachronous MD-IPMNs and nonneoplastic pancreas tissue from the same pancreas from two individuals, and whole human genome microarray analysis was performed. Formalin-fixed paraffin-embedded tissue specimens from 28 distinct IPMNs were then collected from 12 patients, genomic DNA was extracted, and GNAS/KRAS mutational status was investigated. Immunohistochemical analysis was performed to validate the expression pattern of the indicated proteins. Results: Microarray analysis revealed that metachronous MD-IPMNs from the same individual displayed pair-wise correlation coefficients of 0.9523 and 0.9512. In contrast, MD-IPMNs of the same histological grade from different individuals displayed coefficients of 0.8092 and 0.8211. Scatter plot analysis revealed that metachronous MD-IPMNs from the same individual displayed a closer linear relationship. Furthermore, heat map and hierarchical cluster analyses revealed that metachronous MD-IPMNs from the same individual were classified in the same branch, and the gene expression patterns were similar. The GNAS/KRAS mutational statuses of distinct MD-IPMNs were consistent with each other. Immunohistochemical assessment of five specific proteins demonstrated that the same expression pattern between two lesions was observed in 95% of the samples. Conclusions: These findings using molecular analyses indicate that MD-IPMNs might display features of monoclonal skip progression.

元の言語英語
ページ(範囲)969-977
ページ数9
ジャーナルAnnals of Surgery
265
発行部数5
DOI
出版物ステータス出版済み - 5 1 2017

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Pancreatic Neoplasms
Neoplasms
Microarray Analysis
Human Genome
Paraffin
Formaldehyde
Cluster Analysis
Pancreas
Proteins
Hot Temperature
RNA
Gene Expression
DNA

All Science Journal Classification (ASJC) codes

  • Surgery

これを引用

Molecular Evidence for Monoclonal Skip Progression in Main Duct Intraductal Papillary Mucinous Neoplasms of the Pancreas. / Date, Kenjiro; Takao, Ohtsuka; Fujimoto, Takaaki; Tamura, Koji; Kimura, Hideyo; Matsunaga, Taketo; Mochidome, Naoki; Miyazaki, Tetsuyuki; Mori, Yasuhisa; Oda, Yoshinao; Nakamura, Masafumi; Tanaka, Masao.

:: Annals of Surgery, 巻 265, 番号 5, 01.05.2017, p. 969-977.

研究成果: ジャーナルへの寄稿記事

Date, Kenjiro ; Takao, Ohtsuka ; Fujimoto, Takaaki ; Tamura, Koji ; Kimura, Hideyo ; Matsunaga, Taketo ; Mochidome, Naoki ; Miyazaki, Tetsuyuki ; Mori, Yasuhisa ; Oda, Yoshinao ; Nakamura, Masafumi ; Tanaka, Masao. / Molecular Evidence for Monoclonal Skip Progression in Main Duct Intraductal Papillary Mucinous Neoplasms of the Pancreas. :: Annals of Surgery. 2017 ; 巻 265, 番号 5. pp. 969-977.
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title = "Molecular Evidence for Monoclonal Skip Progression in Main Duct Intraductal Papillary Mucinous Neoplasms of the Pancreas",
abstract = "Objective: To clarify clonality of distinct multisegmental main duct (MD)-intraductal papillary mucinous neoplasms (IPMNs) using microarray analysis. Background: IPMNs represent a pancreatic ductal cell field defect, which causes multiple occurrences of lesions. In addtion, it has been speculated that MD-IPMNs display features of monoclonal skip progression. Methods: Total RNA was extracted from fresh-frozen tissue samples of metachronous MD-IPMNs and nonneoplastic pancreas tissue from the same pancreas from two individuals, and whole human genome microarray analysis was performed. Formalin-fixed paraffin-embedded tissue specimens from 28 distinct IPMNs were then collected from 12 patients, genomic DNA was extracted, and GNAS/KRAS mutational status was investigated. Immunohistochemical analysis was performed to validate the expression pattern of the indicated proteins. Results: Microarray analysis revealed that metachronous MD-IPMNs from the same individual displayed pair-wise correlation coefficients of 0.9523 and 0.9512. In contrast, MD-IPMNs of the same histological grade from different individuals displayed coefficients of 0.8092 and 0.8211. Scatter plot analysis revealed that metachronous MD-IPMNs from the same individual displayed a closer linear relationship. Furthermore, heat map and hierarchical cluster analyses revealed that metachronous MD-IPMNs from the same individual were classified in the same branch, and the gene expression patterns were similar. The GNAS/KRAS mutational statuses of distinct MD-IPMNs were consistent with each other. Immunohistochemical assessment of five specific proteins demonstrated that the same expression pattern between two lesions was observed in 95{\%} of the samples. Conclusions: These findings using molecular analyses indicate that MD-IPMNs might display features of monoclonal skip progression.",
author = "Kenjiro Date and Ohtsuka Takao and Takaaki Fujimoto and Koji Tamura and Hideyo Kimura and Taketo Matsunaga and Naoki Mochidome and Tetsuyuki Miyazaki and Yasuhisa Mori and Yoshinao Oda and Masafumi Nakamura and Masao Tanaka",
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TY - JOUR

T1 - Molecular Evidence for Monoclonal Skip Progression in Main Duct Intraductal Papillary Mucinous Neoplasms of the Pancreas

AU - Date, Kenjiro

AU - Takao, Ohtsuka

AU - Fujimoto, Takaaki

AU - Tamura, Koji

AU - Kimura, Hideyo

AU - Matsunaga, Taketo

AU - Mochidome, Naoki

AU - Miyazaki, Tetsuyuki

AU - Mori, Yasuhisa

AU - Oda, Yoshinao

AU - Nakamura, Masafumi

AU - Tanaka, Masao

PY - 2017/5/1

Y1 - 2017/5/1

N2 - Objective: To clarify clonality of distinct multisegmental main duct (MD)-intraductal papillary mucinous neoplasms (IPMNs) using microarray analysis. Background: IPMNs represent a pancreatic ductal cell field defect, which causes multiple occurrences of lesions. In addtion, it has been speculated that MD-IPMNs display features of monoclonal skip progression. Methods: Total RNA was extracted from fresh-frozen tissue samples of metachronous MD-IPMNs and nonneoplastic pancreas tissue from the same pancreas from two individuals, and whole human genome microarray analysis was performed. Formalin-fixed paraffin-embedded tissue specimens from 28 distinct IPMNs were then collected from 12 patients, genomic DNA was extracted, and GNAS/KRAS mutational status was investigated. Immunohistochemical analysis was performed to validate the expression pattern of the indicated proteins. Results: Microarray analysis revealed that metachronous MD-IPMNs from the same individual displayed pair-wise correlation coefficients of 0.9523 and 0.9512. In contrast, MD-IPMNs of the same histological grade from different individuals displayed coefficients of 0.8092 and 0.8211. Scatter plot analysis revealed that metachronous MD-IPMNs from the same individual displayed a closer linear relationship. Furthermore, heat map and hierarchical cluster analyses revealed that metachronous MD-IPMNs from the same individual were classified in the same branch, and the gene expression patterns were similar. The GNAS/KRAS mutational statuses of distinct MD-IPMNs were consistent with each other. Immunohistochemical assessment of five specific proteins demonstrated that the same expression pattern between two lesions was observed in 95% of the samples. Conclusions: These findings using molecular analyses indicate that MD-IPMNs might display features of monoclonal skip progression.

AB - Objective: To clarify clonality of distinct multisegmental main duct (MD)-intraductal papillary mucinous neoplasms (IPMNs) using microarray analysis. Background: IPMNs represent a pancreatic ductal cell field defect, which causes multiple occurrences of lesions. In addtion, it has been speculated that MD-IPMNs display features of monoclonal skip progression. Methods: Total RNA was extracted from fresh-frozen tissue samples of metachronous MD-IPMNs and nonneoplastic pancreas tissue from the same pancreas from two individuals, and whole human genome microarray analysis was performed. Formalin-fixed paraffin-embedded tissue specimens from 28 distinct IPMNs were then collected from 12 patients, genomic DNA was extracted, and GNAS/KRAS mutational status was investigated. Immunohistochemical analysis was performed to validate the expression pattern of the indicated proteins. Results: Microarray analysis revealed that metachronous MD-IPMNs from the same individual displayed pair-wise correlation coefficients of 0.9523 and 0.9512. In contrast, MD-IPMNs of the same histological grade from different individuals displayed coefficients of 0.8092 and 0.8211. Scatter plot analysis revealed that metachronous MD-IPMNs from the same individual displayed a closer linear relationship. Furthermore, heat map and hierarchical cluster analyses revealed that metachronous MD-IPMNs from the same individual were classified in the same branch, and the gene expression patterns were similar. The GNAS/KRAS mutational statuses of distinct MD-IPMNs were consistent with each other. Immunohistochemical assessment of five specific proteins demonstrated that the same expression pattern between two lesions was observed in 95% of the samples. Conclusions: These findings using molecular analyses indicate that MD-IPMNs might display features of monoclonal skip progression.

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