Evidence for etiologic field changes in tongue distant from tumor in patients with squamous cell carcinoma of the oral tongue

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00209805%3A_____%2F23%3A00079134" target="_blank" >RIV/00209805:_____/23:00079134 - isvavai.cz</a>

Result on the web

<a href="https://onlinelibrary.wiley.com/doi/epdf/10.1002/path.6025" target="_blank" >https://onlinelibrary.wiley.com/doi/epdf/10.1002/path.6025</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1002/path.6025" target="_blank" >10.1002/path.6025</a>

Result language

angličtina

Original language name

Evidence for etiologic field changes in tongue distant from tumor in patients with squamous cell carcinoma of the oral tongue

Original language description

Oral cancer is a paradigm of Slaughter&apos;s concept of field cancerization, where tumors are thought to originate within an area of cells containing genetic alterations that predispose to cancer development. The field size is unclear but may represent a large area of tissue, and the origin of mutations is also unclear. Here, we analyzed whole exome and transcriptome features in contralateral tumor-distal tongue (i.e. distant from the tumor, not tumor-adjacent) and corresponding tumor tissues of 15 patients with squamous cell carcinoma of the oral tongue. The number of point mutations ranged from 41 to 237 in tumors and from one to 78 in tumor-distal samples. Tumor-distal samples showed mainly clock-like (associated with aging) or tobacco smoking mutational signatures. Tumors additionally showed mutations that associate with cytidine deaminase AID/APOBEC enzyme activities or a UV-like signature. Importantly, no point mutations were shared between a tumor and the matched tumor-distal sample in any patient. TP53 was the most frequently mutated gene in tumors (67%), whereas a TP53 mutation was detected in only one tumor-distal sample, and this mutation was not shared with the matched tumor. Arm-level copy number variation (CNV) was found in 12 tumors, with loss of chromosome (Chr) 8p or gain of 8q being the most frequent events. Two tumor-distal samples showed a gain of Chr8, which was associated with increased expression of Chr8-located genes in these samples, although gene ontology did not show a role for these genes in oncogenic processes. In situ hybridization revealed a mixed pattern of Chr8 gain and neutral copy number in both tumor cells and adjacent nontumor epithelium in one patient. We conclude that distant field cancerization exists but does not present as tumor-related mutational events. The data are compatible with etiologic field effects, rather than classical monoclonal field cancerization theory. (C) 2022 The Authors. The Journal of Pathology published by John Wiley &amp; Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30204 - Oncology

Project

<a href="/en/project/EF16_019%2F0000868" target="_blank" >EF16_019/0000868: Molecular, cellular and clinical approach to healthy ageing</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2023

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Journal of pathology

ISSN

0022-3417

e-ISSN

1096-9896

Volume of the periodical

259

Issue of the periodical within the volume

1

Country of publishing house

US - UNITED STATES

Number of pages

10

Pages from-to

93-102

UT code for WoS article

000897573600001

EID of the result in the Scopus database

2-s2.0-85143907179