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. 2021 Nov 19;21(1):1245.
doi: 10.1186/s12885-021-09000-2.

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

Satoshi Kawakami  1 , Shinichi Takano  2 , Mitsuharu Fukasawa  1 , Hiroko Shindo  1 , Ei Takahashi  1 , Yoshimitsu Fukasawa  1 , Hiroshi Hayakawa  1 , Natsuhiko Kuratomi  1 , Makoto Kadokura  1 , Naohiro Hosomura  3 , Hidetake Amemiya  3 , Hiromichi Kawaida  3 , Hiroshi Kono  3 , Shinya Maekawa  1 , Daisuke Ichikawa  3 , Nobuyuki Enomoto  1
Affiliations

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

Satoshi Kawakami et al. BMC Cancer. .

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.

Keywords: Gallbladder cancer; Next-generation sequencing; Pancreaticobiliary maljunction; TP53.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Flow chart of this study
Fig. 2
Fig. 2
Gene alterations and clinical characteristics of gallbladder carcinoma. The overall view of detected gene alterations in tissues from resected gallbladder cancer specimens is shown. The boxes in the center panel represent detected gene alterations, including mutations and copy number alterations in each case. The left panel shows gene symbols and the frequencies of mutations in each gene; color-coded gene alterations and clinical characteristics are shown in the right panel. The upper panel shows clinical characteristics of each case and a cluster, which was categorized by gene alterations
Fig. 3
Fig. 3
TP53 mutation in resected tissues. Values of control, PBM (without GBC), non-tumor part of PBM with GBC, and tumor part of PBM with GBC are shown. A The percentages of TP53 mutations in resected tissues are shown. TP53 mutation rate was high in gallbladder carcinoma (GBC) cases with pancreaticobiliary maljunction (PBM), especially in tumor tissues, as compared to PBM patients without carcinoma or control patients with chronic cholecystitis. B The allele frequencies (AFs) of TP53 mutation are shown as boxplots. AFs of TP53 increased from control and PBM to PBM with GBC
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