title: Clinical significance of genome-wide minimally deleted regions in oral squamous cell carcinomas.
abstract: Oral squamous cell carcinoma (OSCC) has the highest rate of increase among male cancers in Taiwan. An understanding of the molecular pathogenesis of this disease as well as the development of prognostic markers for the clinical management of this disease is very important. Thus, a systematic loss of heterozygosity (LOH) analysis was performed to define minimally deleted regions (MDRs) in 63 male OSCCs using 400 polymorphic microsatellite markers. For increasing reliability, genomic DNA was extracted from >90% tumor cells that had been purified by LCM, and only when a microsatellite marker provided LOH information in >30% of the OSCCs was there considered to be successful allelotyping. A correlation of the various MDRs with clinicopathological parameters and prognosis was carried out. In total, 32 MDRs were identified and ten were noted as novel. In addition, six MDRs were found to be associated with cigarette smoking. Among these markers, a loss of MDR c7r2 (7q32.2-q35) was significantly associated with poor disease-free survival (DFS) and ten MDRs were associated with allelic imbalance (AI) in tumors. Among the latter, a loss of MDR c14r1 (14q24.2-q32.12) and c11r1 (11q13.4-q25) had a synergistic effect on poor DFS and were able to reduce further the DFS rate in patients with MDR c7r2 loss. Taken together, the results generated in this study provide new insights that help with exploring the molecular mechanisms associated with OSCC tumorigenesis and cigarette smoking. They also should aid the development of potential prognostic markers for the clinical management of OSCC.
authors.affiliation: Graduate Institute of Biomedical Sciences, Chang Gung University, Tao-Yuan, Taiwan.
authors.forename: Huei-Tzu
authors.initials: HT
authors.lastname: Chien
authors.forename: Chun-Ta
authors.initials: CT
authors.lastname: Liao
authors.forename: Shiang-Fu
authors.initials: SF
authors.lastname: Huang
authors.forename: I-How
authors.initials: IH
authors.lastname: Chen
authors.forename: Tsung-Yun
authors.initials: TY
authors.lastname: Liu
authors.forename: Yuh-Shan
authors.initials: YS
authors.lastname: Jou
authors.forename: Hung-Ming
authors.initials: HM
authors.lastname: Wang
authors.forename: Ling-Ling
authors.initials: LL
authors.lastname: Hsieh
mesh_terms: D000483:Alleles; D022981:Allelic Imbalance; D014408:Biomarkers, Tumor / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D004273:DNA, Neoplasm / Q000032:analysis / Q000235:genetics; D018572:Disease-Free Survival; D017353:Gene Deletion; D016678:Genome; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D012907:Smoking / Q000235:genetics; D013624:Taiwan
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm