Stepwise correlation of TP53 mutations from pancreaticobiliary maljunction to gallbladder carcinoma: a retrospective study

Abstract Background The genetic changes underlying carcinogenesis in patients with risk factors of gallbladder carcinoma (GBC) remains controversial, especially in patients with pancreaticobiliary maljunction (PBM). This study aimed to clarify the association between risk factors of GBC and genetic...

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Autores principales:	Satoshi Kawakami, Shinichi Takano, Mitsuharu Fukasawa, Hiroko Shindo, Ei Takahashi, Yoshimitsu Fukasawa, Hiroshi Hayakawa, Natsuhiko Kuratomi, Makoto Kadokura, Naohiro Hosomura, Hidetake Amemiya, Hiromichi Kawaida, Hiroshi Kono, Shinya Maekawa, Daisuke Ichikawa, Nobuyuki Enomoto
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Gallbladder cancer Pancreaticobiliary maljunction TP53 Next-generation sequencing Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/50820336c5f44c5e8976be95fdb7c97c
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spelling	oai:doaj.org-article:50820336c5f44c5e8976be95fdb7c97c2021-11-21T12:30:20ZStepwise correlation of TP53 mutations from pancreaticobiliary maljunction to gallbladder carcinoma: a retrospective study10.1186/s12885-021-09000-21471-2407https://doaj.org/article/50820336c5f44c5e8976be95fdb7c97c2021-11-01T00:00:00Zhttps://doi.org/10.1186/s12885-021-09000-2https://doaj.org/toc/1471-2407Abstract Background The genetic changes underlying carcinogenesis in patients with risk factors of gallbladder carcinoma (GBC) remains controversial, especially in patients with pancreaticobiliary maljunction (PBM). This study aimed to clarify the association between risk factors of GBC and genetic changes using next-generation sequencing (NGS). Methods We retrospectively analyzed resected tissues of 64 patients who were diagnosed with GBC (n = 26), PBM [with GBC (n = 8), without GBC (n = 20)], and chronic cholecystitis, used as a control group (n = 10). DNA was extracted from tumors and their surrounding tissues, which were precisely separated by laser-capture microdissection. Gene alterations of 50 cancer-related genes were detected by NGS and compared with clinical information, including PBM status. Results The most frequent gene alterations in GBC tissues occurred in TP53 (50%), followed by EGFR (20.6%), RB1 (17.6%), and ERBB2 (17.6%). Gene alterations that were targetable by molecular targeted drugs were detected in 20 cases (58.8%). Statistical analysis of gene alterations and risk factors revealed that TP53 alteration rate was higher in GBC patients with PBM than those without PBM (p = 0.038), and the TP53 mutation rates in the epithelium of control patients, epithelium of PBM patients without GBC, peritumoral mucosa of GBC patients with PBM, and tumor tissue of GBC patients with PBM were 10, 10, 38, and 75%, respectively (p < 0.01). Conclusions TP53 alteration more than KRAS mutation was revealed to underlie carcinogenesis in patients with PBM.Satoshi KawakamiShinichi TakanoMitsuharu FukasawaHiroko ShindoEi TakahashiYoshimitsu FukasawaHiroshi HayakawaNatsuhiko KuratomiMakoto KadokuraNaohiro HosomuraHidetake AmemiyaHiromichi KawaidaHiroshi KonoShinya MaekawaDaisuke IchikawaNobuyuki EnomotoBMCarticleGallbladder cancerPancreaticobiliary maljunctionTP53Next-generation sequencingNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENBMC Cancer, Vol 21, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Gallbladder cancer Pancreaticobiliary maljunction TP53 Next-generation sequencing Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Gallbladder cancer Pancreaticobiliary maljunction TP53 Next-generation sequencing Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Satoshi Kawakami Shinichi Takano Mitsuharu Fukasawa Hiroko Shindo Ei Takahashi Yoshimitsu Fukasawa Hiroshi Hayakawa Natsuhiko Kuratomi Makoto Kadokura Naohiro Hosomura Hidetake Amemiya Hiromichi Kawaida Hiroshi Kono Shinya Maekawa Daisuke Ichikawa Nobuyuki Enomoto Stepwise correlation of TP53 mutations from pancreaticobiliary maljunction to gallbladder carcinoma: a retrospective study
description	Abstract Background The genetic changes underlying carcinogenesis in patients with risk factors of gallbladder carcinoma (GBC) remains controversial, especially in patients with pancreaticobiliary maljunction (PBM). This study aimed to clarify the association between risk factors of GBC and genetic changes using next-generation sequencing (NGS). Methods We retrospectively analyzed resected tissues of 64 patients who were diagnosed with GBC (n = 26), PBM [with GBC (n = 8), without GBC (n = 20)], and chronic cholecystitis, used as a control group (n = 10). DNA was extracted from tumors and their surrounding tissues, which were precisely separated by laser-capture microdissection. Gene alterations of 50 cancer-related genes were detected by NGS and compared with clinical information, including PBM status. Results The most frequent gene alterations in GBC tissues occurred in TP53 (50%), followed by EGFR (20.6%), RB1 (17.6%), and ERBB2 (17.6%). Gene alterations that were targetable by molecular targeted drugs were detected in 20 cases (58.8%). Statistical analysis of gene alterations and risk factors revealed that TP53 alteration rate was higher in GBC patients with PBM than those without PBM (p = 0.038), and the TP53 mutation rates in the epithelium of control patients, epithelium of PBM patients without GBC, peritumoral mucosa of GBC patients with PBM, and tumor tissue of GBC patients with PBM were 10, 10, 38, and 75%, respectively (p < 0.01). Conclusions TP53 alteration more than KRAS mutation was revealed to underlie carcinogenesis in patients with PBM.
format	article
author	Satoshi Kawakami Shinichi Takano Mitsuharu Fukasawa Hiroko Shindo Ei Takahashi Yoshimitsu Fukasawa Hiroshi Hayakawa Natsuhiko Kuratomi Makoto Kadokura Naohiro Hosomura Hidetake Amemiya Hiromichi Kawaida Hiroshi Kono Shinya Maekawa Daisuke Ichikawa Nobuyuki Enomoto
author_facet	Satoshi Kawakami Shinichi Takano Mitsuharu Fukasawa Hiroko Shindo Ei Takahashi Yoshimitsu Fukasawa Hiroshi Hayakawa Natsuhiko Kuratomi Makoto Kadokura Naohiro Hosomura Hidetake Amemiya Hiromichi Kawaida Hiroshi Kono Shinya Maekawa Daisuke Ichikawa Nobuyuki Enomoto
author_sort	Satoshi Kawakami
title	Stepwise correlation of TP53 mutations from pancreaticobiliary maljunction to gallbladder carcinoma: a retrospective study
title_short	Stepwise correlation of TP53 mutations from pancreaticobiliary maljunction to gallbladder carcinoma: a retrospective study
title_full	Stepwise correlation of TP53 mutations from pancreaticobiliary maljunction to gallbladder carcinoma: a retrospective study
title_fullStr	Stepwise correlation of TP53 mutations from pancreaticobiliary maljunction to gallbladder carcinoma: a retrospective study
title_full_unstemmed	Stepwise correlation of TP53 mutations from pancreaticobiliary maljunction to gallbladder carcinoma: a retrospective study
title_sort	stepwise correlation of tp53 mutations from pancreaticobiliary maljunction to gallbladder carcinoma: a retrospective study
publisher	BMC
publishDate	2021
url	https://doaj.org/article/50820336c5f44c5e8976be95fdb7c97c
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Stepwise correlation of TP53 mutations from pancreaticobiliary maljunction to gallbladder carcinoma: a retrospective study

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