Genetic characterization of skull base chondrosarcomas

Abstract

A lthough chondrosarcoma is the third most frequent primary malignancy of bone after myeloma and osteosarcoma, 7 skull base chondrosarcomas (SBCSs) are rare, accounting for only approximately 1% of all chondrosarcomas. 6 In France, intracranial chondrosarcomas account for 0.05% of all brain tumors, 21 and together with chordoma, they account for 0.09% of central nervous system tumors in the United States.5 However, among malignant bone tumors in the skull base, SBCS and chordoma are the 2 major histological types. Distinction of these 2 tumors is important, because SBCSs of the skull base are reported to show significantly better prognosis than chordomas. 1,4 Clinicians and pathologists are occasionally confronted by diagnostic problems caused by radiological and histological overlap between SBCSs and chordomas, especially with the "chondroid" subtype of chordomas. Recently, brachyury, a new immunohistochemical marker for chordoma, has been used to help distinguish chordomas from chondrosarcomas in addition to traditional markers, including cytokeratin and epithelial membrane antigen (EMA). 18Little is known about the genetic characteristics of SBCSs, because unlike for chordomas and extracranial chondrosarcomas, there have been no reports of whole-genome analysis of a case series of SBCSs to date. An early cytogenetic study of a single case of SBCS was described, obJect Although chondrosarcomas rarely arise in the skull base, chondrosarcomas and chordomas are the 2 major malignant bone neoplasms occurring at this location. The distinction of these 2 tumors is important, but this distinction is occasionally problematic because of radiological and histological overlap. Unlike chordoma and extracranial chondrosarcoma, no case series presenting a whole-genome analysis of skull base chondrosarcomas (SBCSs) has been reported. The goal of this study is to clarify the genetic characteristics of SBCSs and contrast them with those of chordomas. methods The authors analyzed 7 SBCS specimens for chromosomal copy number alterations (CNAs) using comparative genomic hybridization (CGH). They also examined IDH1 and IDH2 mutations and brachyury expression. results In CGH analyses, the authors detected CNAs in 6 of the 7 cases, including chromosomal gains of 8q21.1, 19, 2q22-q32, 5qcen-q14, 8q21-q22, and 15qcen-q14. Mutation of IDH1 was found with a high frequency (5 of 7 cases, 71.4%), of which R132S was most frequently mutated. No IDH2 mutations were found, and immunohistochemical staining for brachyury was negative in all cases. coNclusioNs To the best of the authors' knowledge, this is the first whole-genome study of an SBSC case series. Their findings suggest that these tumors are molecularly consistent with a subset of conventional central chondrosarcomas and different from skull base chordomas.

Genomic and transcriptomic characterization of skull base chordoma

“…We observed several common chromosomal aberrations including loss of 1p, 10, and 13 and gain of 7 and 17q in our cohort (Figure 1a), consistent with the previous reports [8, 9]. Both chromosomal gain and loss of 7 and 10, respectively, are common genetic lesions, frequently observed in major malignant tumors including glioblastoma [10, 11], melenoma [12], and prostate cancer, [13] suggesting these alterations could be associated with tumor progression in chordoma as well.…”

Prognostic importance of IDH mutations in chondrosarcoma: An individual patient data meta‐analysis

“…The effect of IDH mutations on patient outcome in this group is limited and most of the included studies did not provide survival data. Kanamori et al 23 reported an insignificant correlation of IDH1 mutation with tumor relapse but only seven patients were enrolled in their study. Additional studies are necessary to elucidate the prognostication of IDH1 / 2 mutations in chondrosarcomas of the head and neck.…”

“…Given the rarity of chondrosarcomas, 8 it was difficult to reach statistical significance when examining the prognosis of this tumor. Most of the published data failed to demonstrate the prognostic impact of IDH mutations in chondrosarcomas 17,23,26 . We incorporated nearly 500 cases of chondrosarcoma and highlighted that IDH mutation is an independent prognostic marker regardless of age, gender, tumor grades, and locations.…”

“…Most of the published data failed to demonstrate the prognostic impact of IDH mutations in chondrosarcomas. 17 , 23 , 26 We incorporated nearly 500 cases of chondrosarcoma and highlighted that IDH mutation is an independent prognostic marker regardless of age, gender, tumor grades, and locations. However, there are a few limitations that need to be addressed.…”

Management of sinonasal and skull base nonmesenchymal chondrosarcoma, a narrative review

“…Recently detection of a variety of genetic differences have been used to characterise CS more thoroughly, e.g. detection of mutations by direct sequencing of isocitrate dehydrogenases 1 and 2 (IDH1/2) (19,20) . CS account for 10-20% of all malignant bone tumours most commonly arising in the long bones and pelvis (2,21,22) .…”