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.

Chromosomal Alterations and Gene Expression Changes Associated with the Progression of Leukoplakia to Advanced Gingivobuccal Cancer

“…The amplifications of 3q, 7p, 8q, 9q, 11q, and 12q, as well as the deletions of 3p, 4q, 8p, and 9p were reported at least three times among 12 aCGH studies on primary OSCC tumors [19], with amplifications of 3q26, 11q13 and 11q22.2 being the most reported CNAs in advanced-stage OSCCs [9], [29], [30]. An extensive review by Gollin outlines established associations of most of these alterations in HNSCC [31].…”

Prognostic significance of TMEM16A, PPFIA1, and FADD expression in invasive ductal carcinoma of the breast

“…Studies on the combination effects of two or more gene amplifications in 11q13 were conducted in oral squamous cell carcinoma [32] and breast cancer [31]. This method takes into account possible unknown interactions of other genes and strengthens statistical power in relatively small study sizes.…”

Deletion polymorphism at chromosome 3q26.1 and oral squamous cell carcinoma

“…Datasets created from the dye-swap experiments were averaged and then further analyzed using CGH Analytics software (version 3.4, Agilent Technologies). Although we were originally investigating the relationship between metastasis and chromosomal aberration, a frequent deletion on chromosome 3 showing up on the array-based CGH analysis was not associated with any clinical features of metastasis (13). This deletion was found in 70% (14/20) of DNA extracts from OSCC tissues samples on the long arm of chromosome 3 (Fig.…”

“…In studying the relationship between OSCC metastasis and chromosomal aberration, we found frequent deletion of a probe on chromosome 3 by array-based comparative genomic hybridization (CGH) analysis of OSCC tissues. The deletion was not related to metastasis (13). The present study further examined how the identified chromosomal deletion relates to OSCC.…”