Assessment of clonality of multisegmental main duct intraductal papillary mucinous neoplasms of the pancreas based on GNAS mutation analysis

Koji Tamura, Takao Ohtsuka, Taketo Matsunaga, Hideyo Kimura, Yusuke Watanabe, Noboru Ideno, Teppei Aso, Tetsuyuki Miyazaki, Kenoki Ohuchida, Shunichi Takahata, Tetsuhide Ito, Yasuhiro Ushijima, Yoshinao Oda, Kazuhiro Mizumoto, Masao Tanaka

研究成果: ジャーナルへの寄稿記事

17 引用 (Scopus)

抄録

Background Main duct intraductal papillary mucinous neoplasms (MD-IPMNs) may occur in 1 or multiple segments of the pancreatic duct. Unlike multifocal branch duct (BD)-IPMNs, the clonality of multisegmental MD-IPMNs remains unclear. GNAS mutations are common and specific for IPMNs, and mutational assessment might be useful to determine the clonality of IPMNs as well as to detect high-risk IPMN with distinct ductal adenocarcinoma (pancreatic ductal adenocarcinoma [PDAC]). Our aim was to clarify clonality using GNAS status in multisegmental MD-IPMNs. Methods We retrospectively reviewed the medical records of 70 patients with MD-IPMN. Histologic subtypes and KRAS/GNAS mutations were investigated, and the clonal relationships among multisegmental MD-IPMNs were assessed. Mutational analysis was performed using high-resolution melting analysis and subsequent Sanger/pyrosequencing. Results Thirteen patients had multiple synchronous and/or metachronous lesions. Seven of these 13 patients had multiple MD-IPMNs; 3 had multiple MD-IPMNs and distinct BD-IPMNs; 1 had multiple MD-IPMNs and a distinct PDAC; 1 had a solitary MD-IPMN, BD-IPMN, and PDAC; and 1 had a solitary MD-IPMN and PDAC. KRAS/GNAS mutations were consistent in 10 of 11 multisegmental MD-IPMNs, whereas MD-IPMNs, BD-IPMNs, and PDACs tended to show different mutational patterns. The frequency of malignant IPMNs was significantly higher in the multisegment cohort; malignant IPMNs constituted 90% (9/10) of the multiple cohort and 56% (32/57) of the solitary cohort (P =.04). Mutant GNAS was more frequently observed in the intestinal subtype (94%) than the others. Conclusion MD-IPMNs can be characterized by monoclonal skip progression. Close attention should be paid to the possible presence of skip areas during or after partial pancreatectomy.

元の言語英語
ページ(範囲)277-284
ページ数8
ジャーナルSurgery (United States)
157
発行部数2
DOI
出版物ステータス出版済み - 2 1 2015

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Pancreatic Neoplasms
Mutation
Neoplasms
Adenocarcinoma
Pancreatic Ducts
Pancreatectomy
Freezing
Medical Records

All Science Journal Classification (ASJC) codes

  • Surgery

これを引用

Assessment of clonality of multisegmental main duct intraductal papillary mucinous neoplasms of the pancreas based on GNAS mutation analysis. / Tamura, Koji; Ohtsuka, Takao; Matsunaga, Taketo; Kimura, Hideyo; Watanabe, Yusuke; Ideno, Noboru; Aso, Teppei; Miyazaki, Tetsuyuki; Ohuchida, Kenoki; Takahata, Shunichi; Ito, Tetsuhide; Ushijima, Yasuhiro; Oda, Yoshinao; Mizumoto, Kazuhiro; Tanaka, Masao.

:: Surgery (United States), 巻 157, 番号 2, 01.02.2015, p. 277-284.

研究成果: ジャーナルへの寄稿記事

Tamura, Koji ; Ohtsuka, Takao ; Matsunaga, Taketo ; Kimura, Hideyo ; Watanabe, Yusuke ; Ideno, Noboru ; Aso, Teppei ; Miyazaki, Tetsuyuki ; Ohuchida, Kenoki ; Takahata, Shunichi ; Ito, Tetsuhide ; Ushijima, Yasuhiro ; Oda, Yoshinao ; Mizumoto, Kazuhiro ; Tanaka, Masao. / Assessment of clonality of multisegmental main duct intraductal papillary mucinous neoplasms of the pancreas based on GNAS mutation analysis. :: Surgery (United States). 2015 ; 巻 157, 番号 2. pp. 277-284.
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title = "Assessment of clonality of multisegmental main duct intraductal papillary mucinous neoplasms of the pancreas based on GNAS mutation analysis",
abstract = "Background Main duct intraductal papillary mucinous neoplasms (MD-IPMNs) may occur in 1 or multiple segments of the pancreatic duct. Unlike multifocal branch duct (BD)-IPMNs, the clonality of multisegmental MD-IPMNs remains unclear. GNAS mutations are common and specific for IPMNs, and mutational assessment might be useful to determine the clonality of IPMNs as well as to detect high-risk IPMN with distinct ductal adenocarcinoma (pancreatic ductal adenocarcinoma [PDAC]). Our aim was to clarify clonality using GNAS status in multisegmental MD-IPMNs. Methods We retrospectively reviewed the medical records of 70 patients with MD-IPMN. Histologic subtypes and KRAS/GNAS mutations were investigated, and the clonal relationships among multisegmental MD-IPMNs were assessed. Mutational analysis was performed using high-resolution melting analysis and subsequent Sanger/pyrosequencing. Results Thirteen patients had multiple synchronous and/or metachronous lesions. Seven of these 13 patients had multiple MD-IPMNs; 3 had multiple MD-IPMNs and distinct BD-IPMNs; 1 had multiple MD-IPMNs and a distinct PDAC; 1 had a solitary MD-IPMN, BD-IPMN, and PDAC; and 1 had a solitary MD-IPMN and PDAC. KRAS/GNAS mutations were consistent in 10 of 11 multisegmental MD-IPMNs, whereas MD-IPMNs, BD-IPMNs, and PDACs tended to show different mutational patterns. The frequency of malignant IPMNs was significantly higher in the multisegment cohort; malignant IPMNs constituted 90{\%} (9/10) of the multiple cohort and 56{\%} (32/57) of the solitary cohort (P =.04). Mutant GNAS was more frequently observed in the intestinal subtype (94{\%}) than the others. Conclusion MD-IPMNs can be characterized by monoclonal skip progression. Close attention should be paid to the possible presence of skip areas during or after partial pancreatectomy.",
author = "Koji Tamura and Takao Ohtsuka and Taketo Matsunaga and Hideyo Kimura and Yusuke Watanabe and Noboru Ideno and Teppei Aso and Tetsuyuki Miyazaki and Kenoki Ohuchida and Shunichi Takahata and Tetsuhide Ito and Yasuhiro Ushijima and Yoshinao Oda and Kazuhiro Mizumoto and Masao Tanaka",
year = "2015",
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pages = "277--284",
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T1 - Assessment of clonality of multisegmental main duct intraductal papillary mucinous neoplasms of the pancreas based on GNAS mutation analysis

AU - Tamura, Koji

AU - Ohtsuka, Takao

AU - Matsunaga, Taketo

AU - Kimura, Hideyo

AU - Watanabe, Yusuke

AU - Ideno, Noboru

AU - Aso, Teppei

AU - Miyazaki, Tetsuyuki

AU - Ohuchida, Kenoki

AU - Takahata, Shunichi

AU - Ito, Tetsuhide

AU - Ushijima, Yasuhiro

AU - Oda, Yoshinao

AU - Mizumoto, Kazuhiro

AU - Tanaka, Masao

PY - 2015/2/1

Y1 - 2015/2/1

N2 - Background Main duct intraductal papillary mucinous neoplasms (MD-IPMNs) may occur in 1 or multiple segments of the pancreatic duct. Unlike multifocal branch duct (BD)-IPMNs, the clonality of multisegmental MD-IPMNs remains unclear. GNAS mutations are common and specific for IPMNs, and mutational assessment might be useful to determine the clonality of IPMNs as well as to detect high-risk IPMN with distinct ductal adenocarcinoma (pancreatic ductal adenocarcinoma [PDAC]). Our aim was to clarify clonality using GNAS status in multisegmental MD-IPMNs. Methods We retrospectively reviewed the medical records of 70 patients with MD-IPMN. Histologic subtypes and KRAS/GNAS mutations were investigated, and the clonal relationships among multisegmental MD-IPMNs were assessed. Mutational analysis was performed using high-resolution melting analysis and subsequent Sanger/pyrosequencing. Results Thirteen patients had multiple synchronous and/or metachronous lesions. Seven of these 13 patients had multiple MD-IPMNs; 3 had multiple MD-IPMNs and distinct BD-IPMNs; 1 had multiple MD-IPMNs and a distinct PDAC; 1 had a solitary MD-IPMN, BD-IPMN, and PDAC; and 1 had a solitary MD-IPMN and PDAC. KRAS/GNAS mutations were consistent in 10 of 11 multisegmental MD-IPMNs, whereas MD-IPMNs, BD-IPMNs, and PDACs tended to show different mutational patterns. The frequency of malignant IPMNs was significantly higher in the multisegment cohort; malignant IPMNs constituted 90% (9/10) of the multiple cohort and 56% (32/57) of the solitary cohort (P =.04). Mutant GNAS was more frequently observed in the intestinal subtype (94%) than the others. Conclusion MD-IPMNs can be characterized by monoclonal skip progression. Close attention should be paid to the possible presence of skip areas during or after partial pancreatectomy.

AB - Background Main duct intraductal papillary mucinous neoplasms (MD-IPMNs) may occur in 1 or multiple segments of the pancreatic duct. Unlike multifocal branch duct (BD)-IPMNs, the clonality of multisegmental MD-IPMNs remains unclear. GNAS mutations are common and specific for IPMNs, and mutational assessment might be useful to determine the clonality of IPMNs as well as to detect high-risk IPMN with distinct ductal adenocarcinoma (pancreatic ductal adenocarcinoma [PDAC]). Our aim was to clarify clonality using GNAS status in multisegmental MD-IPMNs. Methods We retrospectively reviewed the medical records of 70 patients with MD-IPMN. Histologic subtypes and KRAS/GNAS mutations were investigated, and the clonal relationships among multisegmental MD-IPMNs were assessed. Mutational analysis was performed using high-resolution melting analysis and subsequent Sanger/pyrosequencing. Results Thirteen patients had multiple synchronous and/or metachronous lesions. Seven of these 13 patients had multiple MD-IPMNs; 3 had multiple MD-IPMNs and distinct BD-IPMNs; 1 had multiple MD-IPMNs and a distinct PDAC; 1 had a solitary MD-IPMN, BD-IPMN, and PDAC; and 1 had a solitary MD-IPMN and PDAC. KRAS/GNAS mutations were consistent in 10 of 11 multisegmental MD-IPMNs, whereas MD-IPMNs, BD-IPMNs, and PDACs tended to show different mutational patterns. The frequency of malignant IPMNs was significantly higher in the multisegment cohort; malignant IPMNs constituted 90% (9/10) of the multiple cohort and 56% (32/57) of the solitary cohort (P =.04). Mutant GNAS was more frequently observed in the intestinal subtype (94%) than the others. Conclusion MD-IPMNs can be characterized by monoclonal skip progression. Close attention should be paid to the possible presence of skip areas during or after partial pancreatectomy.

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