Pattern of genomic imbalances in oral squamous cell carcinomas with and without an increased copy number of 11q13.

Abstract

Among 23 squamous cell carcinomas (SCC) of the oral cavity which were screened for DNA copy number alterations (CNAs) using comparative genomic hybridization, 14 showed a gain of, and 5 of these 14 even an amplification of band 11q13. Amplification of 11q13 was also detected in three of the four studied SCC cell lines and was confirmed by interphase FISH. The number of CNAs in addition to 11q13 varied from 14 to 47 in these carcinomas. All these tumors had seven other specific CNAs in common, i.e. gain on 1p36.3-36.6, 5p15, 9q34, 12p12-13, 14q32, 19 and 20q, all but one showed also an increase of copy number in 7p22, 8q24, 10q26, 12q26, 15q24-25, 16p, 16q23-24, 17q and 22q12-qter. These imbalances were distinctly rarer in the tumors without CNA in 11q13. Loss of material apparently played a minor role in these tumors with gain of 11q13, the most frequent losses (3p12-14 and 5q21) being present in 10 of the 14 cases and loss of 9p13-21 in 5/14 tumors. The three tumors with the highest number of CNAs in addition to 11q13, were histologically classified as pT4, three of the five tumors with 11q13 amplification were highly node-positive (pN 2b-2c). Two of the pT4 tumors shared as many as 23 specific chromosomal segments affected by CNA. Thus, gain of 11q13, though being found at different stages of karyotypic evolution, is apparently associated with a rather specific pattern of other CNAs and involved in progressed stages of malignancy in oral squamous cell carcinoma. In addition, the proportion of patients deceased within one year after diagnosis was clearly higher in the group whose tumors showed an increased 11q13 copy number as compared to the group without this increase. This could point to an association of gain in 11q13 and aggressiveness of the respective tumor.