Genomic Profiling of Oral Squamous Cell Carcinoma by Array-Based Comparative Genomic Hybridization

Abstract

We designed a study to investigate genetic relationships between primary tumors of oral squamous cell carcinoma (OSCC) and their lymph node metastases, and to identify genomic copy number aberrations (CNAs) related to lymph node metastasis. For this purpose, we collected a total of 42 tumor samples from 25 patients and analyzed their genomic profiles by array-based comparative genomic hybridization. We then compared the genetic profiles of metastatic primary tumors (MPTs) with their paired lymph node metastases (LNMs), and also those of LNMs with non-metastatic primary tumors (NMPTs). Firstly, we found that although there were some distinctive differences in the patterns of genomic profiles between MPTs and their paired LNMs, the paired samples shared similar genomic aberration patterns in each case. Unsupervised hierarchical clustering analysis grouped together 12 of the 15 MPT-LNM pairs. Furthermore, similarity scores between paired samples were significantly higher than those between non-paired samples. These results suggested that MPTs and their paired LNMs are composed predominantly of genetically clonal tumor cells, while minor populations with different CNAs may also exist in metastatic OSCCs. Secondly, to identify CNAs related to lymph node metastasis, we compared CNAs between grouped samples of MPTs and LNMs, but were unable to find any CNAs that were more common in LNMs. Finally, we hypothesized that subpopulations carrying metastasis-related CNAs might be present in both the MPT and LNM. Accordingly, we compared CNAs between NMPTs and LNMs, and found that gains of 7p, 8q and 17q were more common in the latter than in the former, suggesting that these CNAs may be involved in lymph node metastasis of OSCC. In conclusion, our data suggest that in OSCCs showing metastasis, the primary and metastatic tumors share similar genomic profiles, and that cells in the primary tumor may tend to metastasize after acquiring metastasis-associated CNAs.

Genomic Loss of DUSP4 Contributes to the Progression of Intraepithelial Neoplasm of Pancreas to Invasive Carcinoma

“…Genomic DNA was extracted according to the standard proteinase K digestion method, followed by phenol/chloroform extraction and ethanol precipitation. As the reference DNA for array CGH, genomic DNA from normal renal cortex was prepared as described previously (14). Genomic analyses in this study were approved by the Ethics Committee of Oita University Hospital (Approval number: P-07-05 and 437) in accordance with the Ethical Guidelines for Clinical Research of the Japanese Ministry of Health, Labor, and Welfare, 2008 (http://www.mhlw.go.jp/ english/).…”

“…Array CGH analysis was performed using 244 k and 44 k oligonucleotide CGH arrays (Agilent Technologies) for genomic DNA from cancer tissues and cancer cell lines, respectively, as described previously (14). Labeling and hybridization were performed in accordance with the manufacturer's instructions.…”

Characterizing Genetic Transitions of Copy Number Alterations and Allelic Imbalances in Oral Tongue Carcinoma Metastasis

“…Yoshioka et al () recently performed a study similar to ours; they examined CNAs in OSCC patient samples using aCGH (Yoshioka et al, ). The samples investigated in their study were 15 paired PT and MLN tissue samples and 10 non‐metastatic OSCC PTs.…”

Immortalization of epithelial cells in oral carcinogenesis as revealed by genome‐wide array comparative genomic hybridization: A meta‐analysis

“…Strict criteria were applied to obtain the most representative result for the current OSCC meta‐analysis study. In total, 312 OSCC samples from 7 studies met our criteria (Table ).…”

“…Because the various datasets (from the 7 studies) were generated using different array CGH platforms and genome assembly coordination, the assembly version between these datasets differed. Therefore, the start and endpoints of the CNAs were converted to match the latest version of the human genome assembly (hg19/GRCh37) using the University of California, Santa Cruz (UCSC) Liftover tool (University of California, Santa Cruz, California, United States) .…”