title: Combination effects of distinct cores in 11q13 amplification region on cervical lymph node metastasis of oral squamous cell carcinoma.
abstract: Lymph node metastasis (LNM) in oral squamous cell carcinoma (OSCC) is known to associate with a significant decrease of 5-year survival. Genetic factors related to the difference of the LNM status in the OSCC have been not fully elucidated. Array-based comparative genomic hybridization (CGH) with individual gene-level resolution and real-time quantitative polymerase chain reaction (QPCR) were conducted using primary tumor materials resected from 54 OSCC patients with (n=22) or without (n=32) cervical LNM. Frequent gain was observed at the 11q13 region exclusively in patients with cervical LNM, which was confirmed by real-time QPCR experiments using 11 genes (TPCN2, MYEOV, CCND1, ORAOV1, FGF4, TMEM16A, FADD, PPFIA1, CTTN, SHANK2 and DHCR7) in this region. It was revealed that two distinct amplification cores existed, which were separated by a breakpoint between MYEOV and CCND1 in the 11q13 region. The combination of copy number amplification at CTTN (core 2) and/or TPCN2/MYEOV (core 1), selected from each core, was most significantly associated with cervical LNM (P=0.0035). Two amplification cores at the 11q13 region may have biological impacts on OSCC cells to spread from the primary site to local lymph nodes. Further study of a larger patient series should be conducted to validate these results.
authors.affiliation: RadGenomics Project, Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Inage, Chiba 263-8555, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Sugahara
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Michikawa
authors.forename: Kenichi
authors.initials: K
authors.lastname: Ishikawa
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Shoji
authors.forename: Mayumi
authors.initials: M
authors.lastname: Iwakawa
authors.forename: Takahiko
authors.initials: T
authors.lastname: Shibahara
authors.forename: Takashi
authors.initials: T
authors.lastname: Imai
mesh_terms: D015220:Calcium Channels / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology*; D002584:Cervix Uteri / Q000473:pathology*; D002874:Chromosome Mapping / Q000379:methods; D002880:Chromosomes, Human, Pair 11; D055028:Comparative Genomic Hybridization / Q000379:methods; D051356:Cortactin / Q000235:genetics; D005260:Female; D005784:Gene Amplification; D018628:Gene Dosage; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics* / Q000473:pathology*; D016133:Polymerase Chain Reaction / Q000379:methods; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics
chemical_list: C495868:CTTN protein, human; D015220:Calcium Channels; D051356:Cortactin; C407245:MYEOV protein, human; D011518:Proto-Oncogene Proteins; C530224:TPCN2 protein, human