The genomic architectures of tumour-adjacent tissues, plasma and saliva reveal evolutionary underpinnings of relapse in head and neck squamous cell carcinoma
- 6 July 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in British Journal of Cancer
- Vol. 125 (6), 854-864
- https://doi.org/10.1038/s41416-021-01464-0
Abstract
Background Head and neck squamous cell carcinoma (HNSCC) is characterised by a dismal prognosis; nonetheless, limited studies have unveiled the mechanisms underlying HNSCC relapse. Methods Next-generation sequencing was performed to identify the somatic mutations in 188 matched samples, including primary tumours, tumour-adjacent tissues (TATs), pre- and post-operative plasma, saliva and peripheral blood lymphocytes (PBLs) from 27 patients. The evolutionary relationship between TATs and tumours were analysed. The dynamic changes of tumour- and TAT-specific mutations in liquid biopsies were monitored together with survival analysis. Results Alterations were detected in 27 out of 27 and 19 out of 26 tumours and TATs, respectively. TP53 was the most prevalently mutated gene in TATs. Some TATs shared mutations with primary tumours, while some other TATs were evolutionarily unrelated to tumours. Notably, TP53 mutations in TATs are stringently associated with premalignant transformation and are indicative of worse survival (hazard ratio = 14.01). TAT-specific mutations were also detected in pre- and/or post-operative liquid biopsies and were indicative of disease relapse. Conclusions TATs might undergo the processes of premalignant transformation, tumorigenesis and eventually relapse by either inheriting tumorigenic mutations from ancestral clones where the tumour originated or gaining private mutations independent of primary tumours. Detection of tumour- and/or TAT-specific genetic alterations in post-operative biopsies shows profound potential in prognostic use.Keywords
Funding Information
- National Natural Science Foundation of China (81302355, 31601159)
This publication has 62 references indexed in Scilit:
- Cancer statistics, 2013CA: A Cancer Journal for Clinicians, 2013
- Emergence of KRAS mutations and acquired resistance to anti-EGFR therapy in colorectal cancerNature, 2012
- Intratumor Heterogeneity and Branched Evolution Revealed by Multiregion SequencingThe New England Journal of Medicine, 2012
- Fast and accurate long-read alignment with Burrows–Wheeler transformBioinformatics, 2010
- The Ligamp TP53 Assay for Detection of Minimal Residual Disease in Head and Neck Squamous Cell Carcinoma Surgical MarginsClinical Cancer Research, 2009
- Fast and accurate short read alignment with Burrows–Wheeler transformBioinformatics, 2009
- Circulating mutant DNA to assess tumor dynamicsNature Medicine, 2008
- Incidence Trends for Human Papillomavirus–Related and –Unrelated Oral Squamous Cell Carcinomas in the United StatesJournal of Clinical Oncology, 2008
- Surgical margin determination in head and neck oncology: Current clinical practice. The results of an International American Head and Neck Society Member SurveyHead & Neck, 2005
- Field cancerisation of the oral cavity: Comparison of the spectrum of molecular alterations in cases presenting with both dysplastic and malignant lesionsOral Oncology, 1997