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

Area of Science:

• Genomics
• Cancer Biology
• Molecular Oncology

Background:

• Field cancerization is a proposed mechanism for cancer development, suggesting clonal expansion of mutated progenitor cells.
• Existing evidence for this phenomenon, particularly in aerodigestive tract tumors, remains limited.

Purpose of the Study:

• To investigate the genomic and transcriptomic characteristics of field cancerization.
• To analyze synchronous aerodigestive tract tumors to understand the underlying molecular drivers.

Main Methods:

• Deep sequencing analyses were performed on tumor samples.
• Genomic and transcriptomic landscapes were characterized.
• Mutational signature analysis was employed.

Main Results:

• Numerous genetic alterations in cancer-associated genes were identified.
• The hypothesis of founder mutations driving field cancerization was refuted.
• Defective homologous recombination was identified as a common mutational process in synchronous tumors.

Conclusions:

• Field cancerization in aerodigestive tract tumors is characterized by widespread genetic alterations rather than a single founder mutation.
• A common etiologic factor, potentially linked to defective homologous recombination and transcriptomic convergence, may underlie synchronous tumors.
• These findings suggest potential therapeutic opportunities targeting shared molecular pathways.