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

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.

Periosteal chondroma of rib at adulthood

“…Mutation-positive central and periosteal cartilaginous tumors occurred more frequently in the tubular bones of the hands and feet than at other anatomical 90% of the acral-based tumors revealed a mutation, compared to 53.2% of tumors in the long bones of the appendicular skeleton, and 35.1% of those in the flat bones [10]. Other study also support the finding of IDH-1 mutation in periosteal chondromas [11]. When we re-viewed the literature it has been seen that this mutation status does not have any effect on prognosis.…”

Rearrangement of chromosome bands 12q14~15 causing HMGA2-SOX5 gene fusion and HMGA2 expression in extraskeletal osteochondroma

“…Expression of HMGA2 was found in both examined skeletal chondromas: a tumor with a pericentric inv( 12 )(p12q13) expressed a truncated transcript of HMGA2 whereas a tumor carrying a t(2;11)(q37;q13) without visible involvement of 12q expressed the full length HMGA2 transcript ( 38 ). On the other hand, neither conventional RT-PCR nor real-time PCR showed expression of HMGA2 in the examined periosteal chondromas, although two of them had structural aberrations of chromosome bands 12q13~15 ( 39 ).…”

“…It should be emphasized that the role of HMGA2 in chondromatous tumors is still studied only very rudimentary in-as-much as only six soft tissue chondromas, two skeletal chondromas, and three periosteal chondromas have been subjected to this type of analysis ( 38 , 39 ). HMGA2 expression was found in four soft tissue chondromas of which three expressed a truncated transcript of HMGA2 and one the full length transcript 1.…”

Periosteal Chondroma of the Pelvis: An Uncommon Tumor in an Unusual Location

“…In addition, cytogenetic studies of PC have shown a loss of chromosome 6 and rearrangements of 2q37, 4q21-25, and 11q13-15 [ 14 ]. Panagopoulos et al also reported chromosome aberrations of 12q13-15 in two of their four cases [ 12 ]. In existing literature, there has been no association shown between PC and other tumors or family history of cancer.…”

“…The pathogenesis of PC is poorly understood. However, similar to enchondroma, PC frequently harbors heterozygous mutations in isocitrate dehydrogenase (IDH) genes mostly involving IDH1 mutation at R132 [11][12][13]. In addition, cytogenetic studies of PC have shown a loss of chromosome 6 and rearrangements of 2q37, 4q21-25, and 11q13-15 [14].…”