Recurrent 12q13-15 chromosomal aberrations, high frequency of isocitrate dehydrogenase 1 mutations, and absence of high mobility group AT-hook 2 expression in periosteal chondromas

Abstract

Periosteal chondroma is a benign cartilage tumor that accounts for <2% of chondromas. In the present study, four cases of periosteal chondromas were cytogenetically investigated and studied for the expression of high-mobility group AT-hook 2 (HMGA2), mutations in codons 132 of isocitrate dehydrogenase (IDH)1 and 172 of IDH2; mutations -C228T and -C250T in the promoter region of telomerase reverse transcriptase (TERT); and for methylation in the promoter regions of O-6-methylguanine-DNA methyltransferase (MGMT) and cellular retinol binding protein 1 (CRBP1). Chromosome aberrations of 12q13-15 were found in two out of the four tumors, while two had a normal karyotype. Two periosteal chondromas carried the mutation IDH1R132C (CGT>TGT), and two carried the mutation IDH1R132L (CGT>CTT). However, none of the four tumors had methylated MGMT and CRBP1 promoters or mutations at codon 172 of IDH2. In addition, -C228T and -C250T mutations were not present in the promoter region of TERT, nor was HMGA2 demonstrated to be expressed. The present study indicated that in periosteal chondromas, the involvement of 12q13-15 in structural rearrangements may be recurrent but that HMGA2 is not expressed. Additionally, the periosteal chondromas investigated in the study carried a heterozygous IDH1R132 mutation, the MGMT and CRBP1 promoters were not methylated, and -C228T and -C250T mutations in the promoter region of TERT were absent.

Keywords: 12q13-15 chromosomal aberrations; cytogenetics; high-mobility group AT-hook 2; isocitrate dehydrogenase 1 mutations; periosteal chondromas.

Figure 1.

Histology, cytogenetics, HMGA2 expression, and IDH1 mutations in periosteal chondromas. (A) Histologic examination of case 1 exhibiting a nodular tumor of benign chondrocytes covered by periosteum. (B) Partial karyotypes presenting chromosome aberrations der(13)t(12;13)(q13;p11) and der(12)t(12;13)(q13;p11) in case 3, and del(12)(q15q23) in case 4, with the corresponding normal chromosome homologs; breakpoint positions are indicated by arrows. (C) Partial sequence chromatogram displaying the CGT>TGT (IDH1R132C; cases 1 and 2) and CGT>CTT in (IDH1R132L; cases 3 and 4) IDH1. (D) Polymerase chain reaction results demonstrating the amplification of HMGA2 exons 1–3 and S100A10. M, GeneRuler 1 Kb Plus DNA ladder (Thermo Fisher Scientific, Waltham, MA, USA); R, cDNA synthesized from Human Universal Reference Total RNA; B, no RNA in cDNA synthesis. HMGA2, high-mobility group AT-hook 2; IDH, isocitrate dehydrogenase.