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Molecular Characterization of Locally Relapsed Head and Neck Cancer after Concomitant Chemoradiotherapy.
- Source :
-
Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2019 Dec 01; Vol. 25 (23), pp. 7256-7265. Date of Electronic Publication: 2019 Aug 22. - Publication Year :
- 2019
-
Abstract
- Purpose: To investigate the pathobiological origin of local relapse after chemoradiotherapy, we studied genetic relationships of primary tumors (PT) and local relapses (LR) of patients treated with chemoradiotherapy.<br />Experimental Design: First, low-coverage whole genome sequencing was performed on DNA from 44 biopsies of resected head and neck squamous cell carcinoma (HNSCC) specimens (median 3 biopsies/tumor) to assess suitability of copy number alterations (CNAs) as biomarker for genetic relationships. CNAs were compared within and between tumors and an algorithm was developed to assess genetic relationships with consideration of intratumor heterogeneity. Next, this CNA-based algorithm was combined with target enrichment sequencing of genes frequently mutated in HNSCC to assess the genetic relationships of paired tumors and LRs of patients treated with chemoradiotherapy.<br />Results: Genetic relationship analysis using CNAs could accurately (96%) predict tumor biopsy pairs as patient-matched or independent. However, subsequent CNA analysis of PTs and LRs after chemoradiotherapy suggested genetic relationships in only 20% of cases, and absence in 80%. Target enrichment sequencing for mutations confirmed absence of any genetic relationship in half of the paired PTs and LRs.<br />Conclusions: There are minor variations in CNA profiles within different areas of HNSCC tumors and many between independent tumors, suggesting that CNA profiles could be exploited as a marker of genetic relationship. Using CNA profiling and mutational analysis of cancer driver genes, relapses after chemoradiotherapy appear to be partially genetically related to the corresponding PTs, but seem often genetically unrelated. This remarkable observation warrants further studies and will impact therapeutic innovations and prognostic modeling when using index tumor characteristics.<br /> (©2019 American Association for Cancer Research.)
- Subjects :
- Aged
Aged, 80 and over
Female
Follow-Up Studies
Head and Neck Neoplasms genetics
Head and Neck Neoplasms therapy
High-Throughput Nucleotide Sequencing
Humans
Male
Middle Aged
Neoplasm Recurrence, Local genetics
Neoplasm Recurrence, Local therapy
Prognosis
Squamous Cell Carcinoma of Head and Neck genetics
Squamous Cell Carcinoma of Head and Neck therapy
Survival Rate
Biomarkers, Tumor genetics
Chemoradiotherapy mortality
DNA Copy Number Variations
Head and Neck Neoplasms pathology
Mutation
Neoplasm Recurrence, Local pathology
Squamous Cell Carcinoma of Head and Neck pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1557-3265
- Volume :
- 25
- Issue :
- 23
- Database :
- MEDLINE
- Journal :
- Clinical cancer research : an official journal of the American Association for Cancer Research
- Publication Type :
- Academic Journal
- Accession number :
- 31439582
- Full Text :
- https://doi.org/10.1158/1078-0432.CCR-19-0628