Clonal Evolution in head and neck squamous cell carcinoma? Temporal changes of genetic diversity

Recurrent disease is a common threat in head neck squamous cell carcinoma (HNSCC) with often limited treatment options and therefore poor survival rates. Resistance to therapy can be conferred by intratumoral heterogeneity and the emergence of therapy-resistant tumor subclones.

In this study, we analyzed intratumoral genomic alterations in HNSCC patients (n = 5) with recurrent and/or metastatic disease. Samples from 2 – 4 different time points per patient spanning 13 – 88 months were included. Whole exome sequencing was performed on DNA extracted from formalin-fixed and paraffin-embedded tissue (tumor and matched non-malignant tissue). Data was processed by an in-house analysis pipeline.

A high burden of somatic mutations was observed in all tumor samples. Recurrent disease after more than 6 years showed low numbers of shared mutations compared to initial diagnosis, while in cases of rapid disease recurrence the frequency of mutations shared between different time points was generally high. The subset of shared mutations harbored alterations in important tumor suppressor genes including CDKN2A, TP53 or RB1. Notably, no shared mutations were found in one case with repeat biopsies from the same localization.

Our data gives insights into the heterogeneity and plasticity of the genetic landscape of HNSCC after different lines of treatment. Knowledge of individual genomic alterations of target genes or resistance mechanisms is of high importance for patient-tailored molecular therapy approaches.

Publication History

Publication Date:
18 April 2018 (online)