Recurrent genetic aberrations in thymoma and thymic carcinoma

Abstract

Apart from single reported aberrant karyotypes, genetic alterations in thymic epithelial neoplasms have not been investigated so far. In this study, 12 World Health Organization classification type A thymomas (medullary thymomas), 16 type B3 thymomas (well-differentiated thymic carcinomas), and nine type C thymomas, all of them primary thymic squamous cell carcinomas, were analyzed by comparative genomic hybridization and fluorescence in situ hybridization. With the exception of one single case, type A thymomas did not reveal chromosomal gains or losses in comparative genomic hybridization. In contrast, all type B3 thymomas showed chromosomal imbalances, with gain of 1q, loss of chromosome 6, and loss of 13q occurring in 11 (69%), six (38%), and five (31%) of 16 cases, respectively. In primary thymic squamous cell carcinoma, the most frequent chromosomal losses were observed for 16q (six of nine cases, 67%), 6 (4 of 9, 44%), and 3p and 17p (three of nine each, 33%), whereas recurrent gains of chromosomal material were gains of 1q (5 of 9, 56%), 17q, and 18 (three of nine each, 33%). This study shows that the distinct histological thymoma types A and B3 exhibit distinct genetic phenotypes, whereas type B3 thymoma and primary thymic squamous cell carcinoma partially share genetic aberrations. In addition to the possible tumorigenic role, the deletion in type B3 thymoma of chromosome 6, harboring the HLA locus, might play a role in the pathogenesis of paraneoplastic autoimmunity characteristic of thymoma.

Figure 1.

CGH analysis of type A thymoma (medullary thymoma). Out of 12 type A thymomas, only one case showed a chromosomal imbalance detectable by CGH (del 6p21-pter).

Figure 2.

CGH analysis of type B3 thymoma (well-differentiated thymic carcinoma). All 16 type B3 thymomas showed chromosomal imbalances, with gain of 1q, loss of chromosome 6, and loss of 13q occurring in 11 (69%), six (38%), and five (31%) of 16 cases. Bar on the left: loss of chromosomal material; bar on the right: gain of chromosomal material. Thick bar: high-level amplification.

Figure 3.

Fluorescence in situ hybridization of a WHO type B3 thymoma (case13). A: Green signals, centromeric probe for chromosome 11; red signal, centromeric probe for chromosome 6, corresponding to a loss of chromosome 6 observed in this case in CGH. B: Green signals, centromeric probe for chromosome 1; red signal, centromeric probe for chromosome 6, corresponding to a gain of 1q observed in this case in CGH in addition to a loss of chromosome 6.

Figure 4.

CGH analysis of primary thymic squamous cell carcinoma. In primary thymic squamous cell carcinoma, the most frequent chromosomal losses were observed for 16q (six of nine cases, 67%), 6 (four of nine, 44%), 3p and 17p (three of nine each, 33%), whereas recurrent gains of chromosomal material were gains of 1q (five of nine, 56%), 17q and 18 (three of nine each, 33%). Bar on the left: loss of chromosomal material; bar on the right, gain of chromosomal material.