Transcriptomic convergence despite genomic divergence drive field cancerization in synchronous squamous tumors

Front Oncol. 2024 Jun 13:14:1272432. doi: 10.3389/fonc.2024.1272432. eCollection 2024.

Abstract

Introduction: Field cancerization is suggested to arise from imbalanced differentiation in individual basal progenitor cells leading to clonal expansion of mutant cells that eventually replace the epithelium, although without evidence.

Methods: We performed deep sequencing analyses to characterize the genomic and transcriptomic landscapes of field change in two patients with synchronous aerodigestive tract tumors.

Results: Our data support the emergence of numerous genetic alterations in cancer-associated genes but refutes the hypothesis that founder mutation(s) underpin this phenomenon. Mutational signature analysis identified defective homologous recombination as a common underlying mutational process unique to synchronous tumors.

Discussion: Our analyses suggest a common etiologic factor defined by mutational signatures and/or transcriptomic convergence, which could provide a therapeutic opportunity.

Keywords: field cancerization; field change; genomic; synchronous head and neck cancers; transcriptomic.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This initiative is funded by SingHealth Duke-NUS Academic Medical Centre, facilitated by Joint Officer of Academic Medicine (JOAM). It is an initiative of Surgery Academic Clinical Program (SACP) under SACP Seed grant and the Surgeon-Scientist Strategic Start-Up Grant. Furthermore, this work is also supported by NCCS Cancer Fund, NCC Research Fund and SingHealth Oncology Academic Clinical Program under the Cancer Collaborative Scheme. NI is supported by National Medical Research Council Clinician-Scientist Awards (NMRC/CSA-INV/0011/2016 and MOH-000325-00). C-AO is supported by the National Medical Research Council Clinician Scientist-Individual Research Grant (MOH-CIRG21jun-0005) and Clinician Scientist Award (INV category) (MOH-CSAINV22jul-0005).