title: Chromosomal aberrations and prognosis in patients with concomitant chemoradiotherapy for resected head and neck cancer.
abstract: Although concomitant chemoradiotherapy (CCRT) has recently become a mainstay of a primary treatment modality in advanced head and neck squamous cell carcinoma (HNSCC), some of the patients experience CCRT failure. If we can predict the CCRT outcomes, we can reduce unnecessary CCRT avoiding risk of CCRT‑related complication. We aimed to identify genetic alteration markers related to treatment failure in HNSCC patients who underwent radical surgery and CCRT. Genome‑wide copy number alterations (CNAs) were analyzed in 18 HNSCC patients with (n=9) or without (n=9) recurrence using oligoarray‑comparative genomic hybridization and candidate CNAs were validated by quantitative RT‑PCR. A total of 15 recurrently altered regions (RARs) were identified in the 18 HNSCC cases. Among them, two RARs were significantly associated with CCRT‑failure: copy number gained RARs of 7p11.2 harboring EGFR (P=0.029) and 18p11.32 harboring TYMS gene (P=0.029). Three RARs (7p11.2, 9p21.3 and 18p11.32) were significantly associated with poor disease‑specific survival in univariate analysis, and 7p11.2 was consistently significant in the multivariate analysis (HR 40.68, P=0.003). In conclusion, we defined novel genomic alterations associated with CCRT‑failure: 7p11.2 (EGFR) and 18p11.32 (TYMS). Our results provide useful clues for the elucidation of the molecular pathogenesis of HNSCC and to predict CCRT‑failure.
authors.affiliation: Integrated Research Center for Genome Polymorphism College of Medicine, The Catholic University of Korea, Seocho-gu, Seoul 137‑701, Republic of Korea.
authors.forename: Sung-Won
authors.initials: SW
authors.lastname: Park
authors.affiliation: Department of Otolaryngology‑Head and Neck Surgery, College of Medicine, The Catholic University of Korea, Seocho-gu, Seoul 137‑040, Republic of Korea.
authors.forename: Young-Hoon
authors.initials: YH
authors.lastname: Joo
authors.affiliation: Integrated Research Center for Genome Polymorphism College of Medicine, The Catholic University of Korea, Seocho-gu, Seoul 137‑701, Republic of Korea.
authors.forename: Seung-Hyun
authors.initials: SH
authors.lastname: Jung
authors.affiliation: Integrated Research Center for Genome Polymorphism College of Medicine, The Catholic University of Korea, Seocho-gu, Seoul 137‑701, Republic of Korea.
authors.forename: Seon-Hee
authors.initials: SH
authors.lastname: Yim
authors.affiliation: Department of Otolaryngology‑Head and Neck Surgery, College of Medicine, The Catholic University of Korea, Seocho-gu, Seoul 137‑040, Republic of Korea.
authors.forename: In-Chul
authors.initials: IC
authors.lastname: Nam
authors.affiliation: Department of Otolaryngology‑Head and Neck Surgery, College of Medicine, The Catholic University of Korea, Seocho-gu, Seoul 137‑040, Republic of Korea.
authors.forename: Kwang-Jae
authors.initials: KJ
authors.lastname: Cho
authors.affiliation: Department of Otolaryngology‑Head and Neck Surgery, College of Medicine, The Catholic University of Korea, Seocho-gu, Seoul 137‑040, Republic of Korea.
authors.forename: Min-Sik
authors.initials: MS
authors.lastname: Kim
authors.affiliation: Integrated Research Center for Genome Polymorphism College of Medicine, The Catholic University of Korea, Seocho-gu, Seoul 137‑701, Republic of Korea.
authors.forename: Yeun-Jun
authors.initials: YJ
authors.lastname: Chung
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000628:therapy*; D059248:Chemoradiotherapy / Q000379:methods*; D002869:Chromosome Aberrations; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics*; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D018628:Gene Dosage; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000628:therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D000077195:Squamous Cell Carcinoma of Head and Neck; D013940:Thymidylate Synthase / Q000235:genetics; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; C000600377:TYMS protein, human; D013940:Thymidylate Synthase; C512478:EGFR protein, human; D066246:ErbB Receptors