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Stepwise correlation of TP53 mutations from pancreaticobiliary maljunction to gallbladder carcinoma: a retrospective study
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...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8605550/ https://www.ncbi.nlm.nih.gov/pubmed/34798839 http://dx.doi.org/10.1186/s12885-021-09000-2 |
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author | Kawakami, Satoshi Takano, Shinichi Fukasawa, Mitsuharu Shindo, Hiroko Takahashi, Ei Fukasawa, Yoshimitsu Hayakawa, Hiroshi Kuratomi, Natsuhiko Kadokura, Makoto Hosomura, Naohiro Amemiya, Hidetake Kawaida, Hiromichi Kono, Hiroshi Maekawa, Shinya Ichikawa, Daisuke Enomoto, Nobuyuki |
author_facet | Kawakami, Satoshi Takano, Shinichi Fukasawa, Mitsuharu Shindo, Hiroko Takahashi, Ei Fukasawa, Yoshimitsu Hayakawa, Hiroshi Kuratomi, Natsuhiko Kadokura, Makoto Hosomura, Naohiro Amemiya, Hidetake Kawaida, Hiromichi Kono, Hiroshi Maekawa, Shinya Ichikawa, Daisuke Enomoto, Nobuyuki |
author_sort | Kawakami, Satoshi |
collection | PubMed |
description | 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-021-09000-2. |
format | Online Article Text |
id | pubmed-8605550 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-86055502021-11-22 Stepwise correlation of TP53 mutations from pancreaticobiliary maljunction to gallbladder carcinoma: a retrospective study Kawakami, Satoshi Takano, Shinichi Fukasawa, Mitsuharu Shindo, Hiroko Takahashi, Ei Fukasawa, Yoshimitsu Hayakawa, Hiroshi Kuratomi, Natsuhiko Kadokura, Makoto Hosomura, Naohiro Amemiya, Hidetake Kawaida, Hiromichi Kono, Hiroshi Maekawa, Shinya Ichikawa, Daisuke Enomoto, Nobuyuki BMC Cancer Research 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-021-09000-2. BioMed Central 2021-11-19 /pmc/articles/PMC8605550/ /pubmed/34798839 http://dx.doi.org/10.1186/s12885-021-09000-2 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Kawakami, Satoshi Takano, Shinichi Fukasawa, Mitsuharu Shindo, Hiroko Takahashi, Ei Fukasawa, Yoshimitsu Hayakawa, Hiroshi Kuratomi, Natsuhiko Kadokura, Makoto Hosomura, Naohiro Amemiya, Hidetake Kawaida, Hiromichi Kono, Hiroshi Maekawa, Shinya Ichikawa, Daisuke Enomoto, Nobuyuki Stepwise correlation of TP53 mutations from pancreaticobiliary maljunction to gallbladder carcinoma: a retrospective study |
title | 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_short | 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 |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8605550/ https://www.ncbi.nlm.nih.gov/pubmed/34798839 http://dx.doi.org/10.1186/s12885-021-09000-2 |
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