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.
Highlights
Oral squamous cell carcinoma (OSCC), which accounts for more than 90% of all oral cancers, is the most common type of head and neck squamous cell carcinoma (HNSCC), and in 2008 was responsible for about 128,000 deaths worldwide [1]
The highest similarity of genomic profiles was observed between metastatic primary tumors (MPTs) and paired lymph node metastases (LNMs) in 13 out of 15 cases of metastatic oral squamous cell carcinoma (OSCC) (Figure 4)
We found that all of the cases of metastatic OSCC showed some distinctive genomic copy number aberrations (CNAs) patterns between the MPT and paired LNM (Figure S2, S3 and S4)
Summary
Oral squamous cell carcinoma (OSCC), which accounts for more than 90% of all oral cancers, is the most common type of head and neck squamous cell carcinoma (HNSCC), and in 2008 was responsible for about 128,000 deaths worldwide [1]. The presence of cervical lymph node metastasis is associated with a 50% decrease in the 5-year survival of patients with OSCC [2,3]. It is important to detect or predict the presence of lymph node metastasis in order to treat OSCC effectively. Many parameters of the primary tumors, such as size, thickness and altered gene expression [12,13,14,15,16,17,18], have been reported to be useful for identifying nodenegative patients with a high risk of harboring occult node metastasis [18], the mechanisms by which tumor cells spread from the primary site to local lymph nodes are not well understood [19]. Since 1) the break point and patterns of genomic copy number aberrations (CNAs) tend to be reproduced in descendant clones, and 2) genomic aberrations contribute to the malignant behavior of tumor cells by dysregulating the expression of oncogenes or tumor suppressor genes [28], comparison of genomic profiles between a primary tumor and its paired metastasis should provide clues to the process and mechanism of metastasis
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