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. 2022 Jun 7;14(12):2823.
doi: 10.3390/cancers14122823.

Somatic Mutations in Exon 7 of the TP53 Gene in Index Colorectal Lesions Are Associated with the Early Occurrence of Metachronous Adenoma

Tereza Hálková  1 , Renata Ptáčková  1 , Anastasiya Semyakina  1 , Štěpán Suchánek  2   3 , Eva Traboulsi  4 , Ondřej Ngo  5 , Kateřina Hejcmanová  5 , Ondřej Májek  5 , Jan Bureš  3 , Miroslav Zavoral  2   3 , Marek Minárik  1   6   7 , Lucie Benešová  1
Affiliations

Somatic Mutations in Exon 7 of the TP53 Gene in Index Colorectal Lesions Are Associated with the Early Occurrence of Metachronous Adenoma

Tereza Hálková et al. Cancers (Basel). .

Abstract

(1) Background: this prospective study was focused on detailed analysis of the mutation heterogeneity in colorectal lesions removed during baseline (index) colonoscopy to identify patients at high risk of early occurrence of metachronous adenomas. (2) Methods: a total of 120 patients after endoscopic therapy of advanced colorectal neoplasia size ≥10 mm (index lesion) with subsequent surveillance colonoscopy after 10-18 months were included. In total, 143 index lesions and 84 synchronous lesions in paraffin blocks were divided into up to 30 samples. In each of them, the detection of somatic mutations in 11 hot spot gene loci was performed. Statistical analysis to correlate the mutation profiles and the degree of heterogeneity of the lesions with the risk of metachronous adenoma occurrence was undertaken. (3) Results: mutation in exon 7 of the TP53 gene found in the index lesion significantly correlated with the early occurrence of metachronous adenoma (log-rank test p = 0.003, hazard ratio 2.73, 95% confidence interval 1.14-6.56). We did not find an association between the risk of metachronous adenomas and other markers monitored. (4) Conclusions: the findings of this study could lead to an adjustment of existing recommendations for surveillance colonoscopies in a specific group of patients with mutations in exon 7 of the TP53 gene in an index lesion, where a shortening of surveillance interval may be warranted.

Keywords: TP53; colonoscopy; colorectal adenomas; colorectal cancer; index lesion; metachronous lesion; synchronous lesion; tumor heterogeneity.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript or in the decision to publish the results.

Figures

Figure 1
Figure 1
Workflow scheme used for detailed characterization of index and synchronous colorectal lesions.
Figure 2
Figure 2
Mutations in exon 7 of the TP53 gene found in the index lesion as a predictor of metachronous adenoma. Kaplan–Meier survival curves: observed event—detection of adenoma at surveillance colonoscopy in patients with versus without mutation in exon 7 of the TP53 gene.
See this image and copyright information in PMC

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