Molecular cytogenetic characterization of tenosynovial giant cell tumors

Abstract

Tenosynovial giant cell tumor (TSGCT) is a disease of disputed etiology and pathogenesis. Some investigations indicate a neoplastic origin of the tumors; others indicate that they are polyclonal and inflammatory. The cytogenetic and molecular genetic features of TSGCTs are largely unknown, as only some 20 localized and 30 diffuse tumors with cytogenetic aberrations have been reported. The most common karyotypic aberrations have been trisomy for chromosomes 5 and 7 and translocations involving chromosomal area 1p11-13. We decided to screen the genomes of TSGCTs by comparative genomic hybridization (CGH) to perform interphase fluorescence in situ hybridization (IP-FISH), looking for numerical aberrations of chromosomes 1, 5, and 7, and to analyze the tumors for microsatellite instability. Except for two diffuse TSGCTs that came fresh to us, and which, by karyotyping, exhibited t(1;22)(p13;q12) and a t(1;1)(q21;p11) and +7, respectively, all studies had to be performed on formalin-fixed, paraffin-embedded material. DNA was extracted from 51 localized and nine diffuse TSGCTs. CGH was successful for 24 tumors, but none of them showed copy number changes. The IP-FISH studies showed trisomy 7 in 56% of the tumors (15/27), whereas chromosomes 1 and 5 seemed to be disomic in all TSGCTs. All informative tumors were wild-type by microsatellite instability analysis.

Figure 1

(A) Partial karyotype from the diffuse TSGCT of case 46-02 showing normal chromosomes 1 and 22 paired up with the derivative chromosomes 1 and 22 resulting from the t(1;22)(p13;q12) that was the only chromosomal aberration of this case. (B) Partial karyotype from the diffuse TSGCT of case 59-02 showing the two copies of chromosome 1 resulting from a t(1;1)(q21;p11), the only structural chromosomal aberration of this case.

Figure 2

IP-FISH image from case 14-02 showing three signals for the FITC-labeled (green) chromosome 7-specific probe and two signals for the Texas Red-labeled (red) chromosome 1-specific probe.