Comparative genomic hybridization reveals genetic progression of oral squamous cell carcinoma from dysplasia via two different tumourigenic pathways.

To clarify the genetic pathway(s) involved in the development and progression of oral squamous cell carcinoma (OSCC), as well as the relationship between genetic aberrations and biological characteristics of OSCC tumours, comparative genomic hybridization was used to analyse genetic alterations in both primary OSCCs and adjacent dysplastic lesions of the same biopsy specimens from 35 patients. Gain of 8q22-23 was the most frequent alteration in both OSCC and mild dysplasia, and was considered the earliest event in the process of oral tumourigenesis. The average number of DNA sequence copy number aberrations (DSCNAs) increased with progression from mild dysplasia to invasive carcinoma (r = 0.737, n = 70, p < 0.001). OSCC samples were classified as having a large or small number of DSCNAs (OSCC-L, 21.4 +/- 4.7 DSCNAs or OSCC-S, 10.0 +/- 1.7 DSCNAs, respectively; p < 0.0001). Gains of 3q26-qter, 8q, 11q13, 14q, and 20q and losses of 4q, 5q12-22, 6q, 8p, 13q, and 18q22-qter were common to OSCC-L and OSCC-S. Gains of 5p15, 7p, 17q11-22, and 18p and losses of 3p14-21, 4p, and 9p were detected exclusively in OSCC-L. The average number of DSCNAs depended on whether the samples showed OSCC- L or dysplasia plus OSCC-L, or showed OSCC-S or dysplasia plus OSCC-S (p = 0.001). Gain of 5p15 and losses of 4p and 9p were detected even in dysplastic lesions adjacent to OSCC-L samples. Loss of 4p was associated with node metastasis by multivariate analysis (p = 0.013). OSCC-L tumours were more often T3-T4 stage tumours than T1-T2 stage tumours (p = 0.03). These findings suggest that two different types of OSCC, OSCC-L associated with high-stage cancer and OSCC-S associated with low-stage cancer, arise from different types of dysplasia via different genetic pathways.

The relationship of genetic aberrations detected by comparative genomic hybridization to DNA ploidy and tumor size in human oral squamous cell carcinomas.

We have examined genetic alterations in 11 surgically removed oral squamous cell carcinomas (OSCCs) using comparative genomic hybridization (CGH) and laser scanning cytometry (LSC), which allow quantitative analysis of chromosomal abnormalities. CGH analysis revealed gains and/or losses of DNA sequence copy number in all tumors. Gains in DNA sequence copy number were detected frequently for chromosome arms 3q25-28 (6/11), 5p (6/11) and 8q (5/11), and losses in chromosome arms 18q (4/11), 19q (4/11), 17p (3/11), and 19p (3/11). Amplification of 5p was observed in two tumors. LSC detected DNA aneuploidy with DNA indices ranging from 1.30 to 1.82 in 6 of 11 tumors. The number of chromosomal aberrations was higher in DNA aneuploid tumors than in diploid tumors (8.17 vs 3.60/tumor, P<0.05). Furthermore, the average number of chromosomal aberrations was significantly higher in stage T2 tumors and larger tumors than in stage T1 tumors (7.71 vs 3.25/tumor, P<0.05). Our results suggest that DNA aneuploidy and large tumor size reflect an underlying chromosomal instability.

Identification of genetic aberrations in cell lines from oral squamous cell carcinomas by comparative genomic hybridization.

We detected genetic alterations in 14 cell lines established from 14 human oral squamous cell carcinomas (OSCCs) using comparative genomic hybridization (CGH), which allows a comprehensive analysis of chromosomal imbalances and identification of nonrandom genetic aberrations specific to OSCCs. All cell lines showed gains and losses of DNA copy number. DNA losses were detected for chromosomes 18q (10/14) and 4q (9/14) with minimal overlapping regions of 18q12-32 and 4q31-qter, respectively. In contrast, the common sites for increased copy number were chromosomes 5p (12/14), 8q23-ter (11/14), 20p (8/14), 20q (8/14), and 3q25-ter (7/14). These results suggest that losses of 18q12-22 and 4q31-ter and gains of 5p and 8q23-ter play important roles in the development and/or progression of OSCC.

Increased polysomy 3 and 17 detected by fluorescence in situ hybridization (FISH) in oral squamous cell carcinoma.

Numerical chromosome aberrations were studied by fluorescence in situ hybridization (FISH) using pericentromeric DNA probes specific for chromosomes 3 and 17 in 18 oral squamous cell carcinomas (SCCs) and 3 lymph nodes as control. Disomy 3 and 17 was detected in approximately 90% of control cells, and in 60.9 +/- 4.0% and 62.7 +/- 3.6% of SCCs, respectively. Polysomy 3 and 17 significantly increased in SCCs when compared to controls. The pattern of chromosome aberrations varied considerably between cases. There was no obvious relationship between the degree of polysomies and clinicopathological factors such as tumor-differentiation, stage of the disease and clinical outcome. Chromosome aberrations by FISH did not correlate with DNA aneuploidy by flow cytometry. Our results indicate that oral SCCs are more frequently associated with the increased copy number of chromosomes 3 and 17 than previously thought, and that a correlation between chromosome aberrations by FISH and DNA aneuploidy by flow cytometry is not obvious.