Chondrogenic tumors
2022-11-30 Paola Dal Cin, PhD , Judith VMG Bovée Affiliation1.Brigham and Women's Hospital , Harvard Medical School, Boston , MA (USA)
2.Leiden University Medical Center, Leiden, The Netherlands
Classification
Definition
Chondrogenic tumors are the most frequent primary bone tumors. Benign chondrogenic bone tumors are frequent incidental findings at imaging. However, some lesions previously thought to be reactive are locally aggressive and demonstrate reproducible molecular abnormalities. 1 Radiological parameters may be helpful for identification, characterization, and differential diagnosis. 2 Chondrosarcomas are a heterogeneous group of tumors and together constitute the third most common primary malignancy of bone accounting for 20 -27% of primary malignant osseous neoplasms. 3,4 Isocitrate dehydrogenase 1 (IDH1) and 2 (IDH2) mutations in cartilaginous tumors are relatively specific for enchondroma and conventional central chondrosarcoma. 5
| Chondrogenic tumors | Genetic marker(s) |
|---|---|
| Subungual exostosis | t(X;6)(q24-q26;q15-q25), mainly as the sole aberration, 1,2 with breakpoints near by COL12A1 and IRSA, without any fusion transcript product. 3 |
| Bizarre parosteal osteochondromatous proliferation (BPOP) | Recurrent abnormalities as t(1;7)(q32;q21) 4 and inv(7)(q22q32) paired with inv(6)(p25q15). 5 |
| Periosteal chondroma | IDH1(p.Arg132Cys) the most common mutation, 6 12q13-15 rearrangements may be recurrent but that HMGA2 is not expressed. 7 No recurrent chromosome aberrations. 8 |
| Enchondroma | IDH1 (p.Arg132) or IDH2 ( p.Arg172) in 52 % of sporadic cases, 9,10and in 90% of enchondromas in patients with enchondromatosis, 11 either Ollier disease OMIM:16600 or Maffucci syndrome OMIM:614569 |
| Osteochondroma | Chromosome aberrations involving 8q22-q24 EXT1 or 11p11.2 EXT2.12,13 Biallelic inactivation of EXT1 (80% in sporadic tumors) or EXT2.9 |
| Chondroblastoma | H3-3B p.Lys36Met mutation more frequent than in H3-3A. 10,14,15 No recurrent chromosome aberrations. 16 |
| Chondromyxoid fibroma | Heterogeneous and complex rearrangements of 6q24 region identified GRM1 recombined with several 5' partners FRMD6, MYO1E and MEF2A. 17,18 |
| Osteochondromyxoma | Inactivating mutations in PRKAR1A.19,20 |
| Synovial chondromatosis | Diploid or near-diploid abnormal clones with recurrent involvement of chromosome 6. 21 Rearrangements of FN1 and/or ACVR2A, in both benign and malignant lesions. 22,23 Single case with FN1::NFATC2 fusion. 23 |
| Central atypical cartilaginous (ACT) / chondrosarcoma grade 1 (CS1) | Heterozygous point mutations in IDH1 (predominanly p.Arg132C) and IDH2 10 in 50% of the cases |
| Secondary peripheral atypical cartilagenous tumors (ACT)/ chondrosarcoma grade 1 (CS1) | Homozygous deletions of EXT1or EXT2 are much less frequently (40%), 24 with other genetic factor involved e.g. CDKN2A 25,26 |
| Central Chondrosarcoma , grade 2 and 3 | Beside complex karyotypes 27 and IDH1 or IDH1 mutations in ~50% cases, 9 as mechanism of progression from echondroma: additional alterations in the signaling pathways of p53, RB1 , mTOR, Hedgehog, SRC and AKT. 28 Mutations of COL2A1 and TP53 been the most fequent, and less frequently YEATS2, EGFR,NRAS and IHH signaling. 29-31 |
| Secondary peripheral chondrosarcoma, grade 2 and 3 | Chromosomal instability and complex karyotypes. 32,33 Additional non-specific alterations in p53 and RB1 pathways. 33 IDH1 ,IDH2 and NRAS mutations are absent. 9 |
| Periosteal chondrosarcoma | IDH1 and IDH2 mutations in a subset 34,35 |
| Clear cell chondrosarcoma | Clonal aberration in diploid or near diploid karyotype with abnormalities of chr.9 /-9, but not CDKN2A alteration 36 and gain chr. 20 been the most frequent. 37 Single case with H3-3B p.Lis36Met mutation. 14 |
| Mesenchymal chondrosarcoma | HEY1::NCOA2 fusion, arising froma cryptic del(8)(q13.3q21.1) in almost all cases. 38 Single case report with t(1;5)(q42;q32) associated with IRF2BP2::CDX1 fusion. 39 |
| Dedifferentiated chondrosarcoma | Complex karyoype by microarray, including loss 17p (TP53).36 IDH1 or IDH2 mutations,COL2A1, and TERT promoter mutations being common in dedifferentiated chondrosarcoma as likely early events in progression, whereas inactivating mutation of TP53 and high-level copy number alterations may be later events in the dedifferentiated phenotype. 40 |
Article Bibliography
| Reference Number | Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|---|
| 1 | 9885985 | 1999 | Clonal chromosome abnormalities in a so-called Dupuytren's subungual exostosis. | Dal Cin P et al |
| 2 | 15252309 | 2004 | Distinct chromosomal rearrangements in subungual (Dupuytren) exostosis and bizarre parosteal osteochondromatous proliferation (Nora lesion). | Zambrano E et al |
| 3 | 20340132 | 2011 | The t(X;6) in subungual exostosis results in transcriptional deregulation of the gene for insulin receptor substrate 4. | Mertens F et al |
| 4 | 15926071 | 2005 | Bizarre parosteal osteochondromatous proliferation with a t(1;17) translocation. | Endo M et al |
| 5 | 24412018 | 2013 | Bizarre parosteal osteochondromatous proliferation: a new cytogenetic subgroup characterized by inversion of chromosome 7. | Broehm CJ et al |
| 6 | 2198255 | 1990 | Genetic and behavioral analysis of flagellar switch mutants of Salmonella typhimurium. | Magariyama Y et al |
| 7 | 26170993 | 2015 | 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. | Panagopoulos I et al |
| 8 | 21536235 | 2011 | Cytogenetic findings in 14 benign cartilaginous neoplasms. | Sakai Junior N et al |
| 9 | 21598255 | 2011 | IDH1 and IDH2 mutations are frequent events in central chondrosarcoma and central and periosteal chondromas but not in other mesenchymal tumours. | Amary MF et al |
| 10 | 31728625 | 2020 | Mutation-driven epigenetic alterations as a defining hallmark of central cartilaginous tumours, giant cell tumour of bone and chondroblastoma. | Venneker S et al |
| 11 | 32253147 | 2020 | Multiple hereditary exostoses and enchondromatosis. | Jurik AG et al |
| 12 | 9576285 | 1998 | Clonal karyotypic abnormalities of the hereditary multiple exostoses chromosomal loci 8q24.1 (EXT1) and 11p11-12 (EXT2) in patients with sporadic and hereditary osteochondromas. | Bridge JA et al |
| 13 | 21703028 | 2011 | Breakpoint characterization of large deletions in EXT1 or EXT2 in 10 multiple osteochondromas families. | Jennes I et al |
| 14 | 24162739 | 2013 | Distinct H3F3A and H3F3B driver mutations define chondroblastoma and giant cell tumor of bone. | Behjati S et al |
| 15 | 26844533 | 2016 | The H3F3 K36M mutant antibody is a sensitive and specific marker for the diagnosis of chondroblastoma. | Amary MF et al |
| 16 | 19903358 | 2009 | A balanced t(5;17) (p15;q22-23) in chondroblastoma: frequency of the re-arrangement and analysis of the candidate genes. | Romeo S et al |
| 17 | 20696777 | 2010 | Heterogeneous and complex rearrangements of chromosome arm 6q in chondromyxoid fibroma: delineation of breakpoints and analysis of candidate target genes. | Romeo S et al |
| 18 | 24658000 | 2014 | GRM1 is upregulated through gene fusion and promoter swapping in chondromyxoid fibroma. | Nord KH et al |
| 19 | 10973256 | 2000 | Mutations of the gene encoding the protein kinase A type I-alpha regulatory subunit in patients with the Carney complex. | Kirschner LS et al |
| 20 | 28008382 | 2016 | Osteochondromyxoma: Review of a rare carney complex criterion. | Golden T et al |
| 21 | 12550753 | 2003 | Chromosome 6 abnormalities are recurrent in synovial chondromatosis. | Buddingh EP et al |
| 22 | 31273315 | 2019 | Synovial chondromatosis and soft tissue chondroma: extraosseous cartilaginous tumor defined by FN1 gene rearrangement. | Amary F et al |
| 23 | 31589790 | 2020 | A molecular study of synovial chondromatosis. | Agaram NP et al |
| 24 | 21804604 | 2012 | Secondary peripheral chondrosarcoma evolving from osteochondroma as a result of outgrowth of cells with functional EXT. | de Andrea CE et al |
| 25 | 25644707 | 2015 | Cell cycle deregulation and mosaic loss of Ext1 drive peripheral chondrosarcomagenesis in the mouse and reveal an intrinsic cilia deficiency. | de Andrea CE et al |
| 26 | 30519452 | 2018 | Chondrosarcoma: biology, genetics, and epigenetics. | Chow WA et al |
| 27 | 1179337 | 1975 | [Haukeland project. Information and views]. | Heimann P et al |
| 28 | 18624751 | 2009 | Central chondrosarcoma progression is associated with pRb pathway alterations: CDK4 down-regulation and p16 overexpression inhibit cell growth in vitro. | Schrage YM et al |
| 29 | 23770606 | 2013 | Frequent mutation of the major cartilage collagen gene COL2A1 in chondrosarcoma. | Tarpey PS et al |
| 30 | 25024164 | 2014 | Unique mutation portraits and frequent COL2A1 gene alteration in chondrosarcoma. | Totoki Y et al |
| 31 | 29581779 | 2018 | IDH1/2 Mutations Predict Shorter Survival in Chondrosarcoma. | Lugowska I et al |
| 32 | 10502300 | 1999 | Characterization of fertilization-modulated myelin basic protein kinases from sea star: regulation of Mapk. | Lefebvre DL et al |
| 33 | 19336518 | 2009 | Genomic profiling of chondrosarcoma: chromosomal patterns in central and peripheral tumors. | Hallor KH et al |
| 34 | 21596255 | 2011 | Evaluation of Scheimpflug imaging parameters in subclinical keratoconus, keratoconus, and normal eyes. | Uçakhan ÖÖ et al |
| 35 | 25648524 | 2015 | Periosteal chondrosarcoma: a histopathological and molecular analysis of a rare chondrosarcoma subtype. | Cleven AH et al |
| 36 | 22674453 | 2012 | Genetic characterization of mesenchymal, clear cell, and dedifferentiated chondrosarcoma. | Meijer D et al |
| 37 | 15138578 | 2004 | Cytogenetic and spectral karyotype analyses of benign and malignant cartilage tumours. | Sjögren H et al |
| 38 | 22034177 | 2012 | Identification of a novel, recurrent HEY1-NCOA2 fusion in mesenchymal chondrosarcoma based on a genome-wide screen of exon-level expression data. | Wang L et al |
| 39 | 23185413 | 2012 | Whole-transcriptome sequencing identifies novel IRF2BP2-CDX1 fusion gene brought about by translocation t(1;5)(q42;q32) in mesenchymal chondrosarcoma. | Nyquist KB et al |
| 40 | 3314733 | 1987 | Disseminated cicatricial pemphigoid in a child and in an adult. Ultrastructural diagnostic criteria and differential diagnosis with special reference to acquired epidermolysis bullosa. | Hausser I et al |
Citation
Paola Dal Cin, PhD ; Judith VMG Bovée
Chondrogenic tumors
Atlas Genet Cytogenet Oncol Haematol. 2022-11-30
Online version: http://atlasgeneticsoncology.org/solid-tumor/208968/chondrogenic-tumors
