Genetic abnormalities associated with chemoradiation resistance of head and neck squamous cell carcinoma.
OBJECTIVE
To identify reliable predictors of chemoradiation resistance of advanced head and neck squamous cell carcinoma (HNSCC).


METHODS
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.
van den Broek
Guido B
GB
Department of Head and Neck Oncology and Surgery, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands. g.vd.broek@nki.nl
Wreesmann
Volkert B
VB
van den Brekel
Michiel W M
MW
Rasch
Coen R N
CR
Balm
Alfons J M
AJ
Rao
Pulivarthi H
PH
D000970:Antineoplastic Agents / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics* / Q000532:radiotherapy; D002869:Chromosome Aberrations; D003131:Combined Modality Therapy; D004273:DNA, Neoplasm / Q000235:genetics; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D018628:Gene Dosage; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000532:radiotherapy; D006801:Humans; D008297:Male; D009693:Nucleic Acid Hybridization; D011836:Radiation Tolerance / Q000235:genetics*; D032681:Spectral Karyotyping
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm