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Genetic Abnormalities Associated with Chemoradiation Resistance of Head and Neck Squamous Cell Carcinoma

Authors' Affiliations: ¹ Department of Head and Neck Oncology and Surgery and ² Department of Radiation Oncology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital; ³ Department of Otorhinolaryngology-Head and Neck Surgery, Amsterdam Medical Center, Amsterdam, the Netherlands; and ⁴ Department of Pediatrics, Baylor College of Medicine, Houston, Texas

Requests for reprints: Guido B. van den Broek, Department of Head and Neck Oncology and Surgery, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands. Phone: 31-20-5122550; Fax: 31-20-5122554; E-mail: g.vd.broek{at}nki.nl.

Purpose: To identify reliable predictors of chemoradiation resistance of advanced head and neck squamous cell carcinoma (HNSCC).

Experimental Design: We did a matched-pair analysis of 20 chemoradiation-resistant and 20 sensitive HNSCCs, identified among a series of 104 consecutively treated cases. We compared the global DNA copy number profiles derived from comparative genomic hybridization analysis of both groups to identify genetic markers associated with chemoradiation resistance.

Results: Although sensitive and resistant case groups were characterized by a similar total number of genetic aberrations, high-level amplifications were more frequent in resistant tumors. Resistant tumors were characterized by a different profile of genetic changes. Gains of 3q11-q13, 3q21-q26.1, and 6q22-q27 and losses of 3p11-pter and 4p11-pter were significantly associated with chemoradiation resistance. High-level amplifications unique to resistant cases involved the chromosomal regions 1p32, 3q24, 7p11.1, 7p11.2-12, 8p11.1, 8p11.1-12, 12q15, 13q21, 15q12, 18p11.3, and 18q11.

Conclusions: Sensitive and resistant HNSCCs are characterized by divergent genomic profiles. These profiles may be valuable as predictive markers of treatment failure.