Osteogenic tumors

2022-03-04   Judith VMG Bovée , Paola Dal Cin 

1.Leiden University Medical Center, Leiden, The Netherlands
2.Brigham and Women's Hospital , Harvard Medical School, Boston , MA (USA)



Bone-forming (osteogenic) neoplasms are characterized by the formation of osteoid or mature bone directly by the tumor cells.  Osteosarcoma is the most common malignant mesenchymal bone tumor, most prevalent in teenagers and young adults.  Histological variants may pose diagnostic dilemmas and can be missed or confused with other lesions. 1

Osteogenic tumors Genetic marker(s)
OsteomaNo specific genetic findings so far
Osteoid osteoma FOS(14q24.3) and , rarely, FOSB (19q13.3) rearrangements. 2-4
Osteoblastoma (OB)FOS fused with ANKH, CEMIP, MYO1B, IGR and RUNX2; and FOSB rearranged with PPP1R10. 2,4,5 Recurrent 22q deletion activating Wnt/Beta-Catenin signaling pathway 6. Single case with t(1;2;14) (q42;q13;q24) 7.
Low grade central osteosarcoma (LGCO)Amplification of 12q13-q15 region, including MDM2 and CDK4.8,9
OsteosarcomaComplex karyotype with many amplifications, deletions and random translocations, with very few recurrent alterations. Chromosomal instability either by chromothripsis, 10 or by kataegis mechanisms. 11,12T he most common being alterations in genes involved in maintaining genomic stability, as TP53 , RB1 , ATRX and homologous recombination, DNA repair pathway or hormonal signalling (IGF and ER signalling). 4,13-15 Certain hereditary syndromes predispose to osteosarcoma. 4,16
Parosteal osteosarcomaOne or more supernumerary ring chromosome, mainly, as the sole chromosome aberration, containing amplification of 12q13-q15 region, 17,18 including MDM2 and CDK4.8,19
Periosteal osteosarcomaComplex chromosomal alterations and TP53 point mutations , similar to high-grade osteosarcomas 15,20
High -grade surface osteosarcoma No specific genetic findings so far
Secondary osteosarcomaRadiation-associated osteosarcoma show different signature than sporadic osteosarcomma, with losses more frequent than gains chromosome regions.21


Reference NumberPubmed IDLast YearTitleAuthors
1334805992021The 2020 WHO Classification of Tumors of Bone: An Updated Review.Choi JH et al
2298585762018Recurrent rearrangements of FOS and FOSB define osteoblastoma.Fittall MW et al
3305826582019An update of molecular pathology of bone tumors. Lessons learned from investigating samples by next generation sequencing.Baumhoer D et al
4317410492020What's new in bone forming tumours of the skeleton?Franceschini N et al
5321080382020FOS-ANKH and FOS-RUNX2 Fusion Genes in Osteoblastoma.Panagopoulos I et al
6242361972013Recurrent chromosome 22 deletions in osteoblastoma affect inhibitors of the Wnt/beta-catenin signaling pathway.Nord KH et al
7199631182009Osteoblastoma characterized by a three-way translocation: report of a case and review of the literature.Giannico G et al
8213362602011MDM2 and CDK4 immunohistochemistry is a valuable tool in the differential diagnosis of low-grade osteosarcomas and other primary fibro-osseous lesions of the bone.Dujardin F et al
9300012402018Consistent Amplification of FRS2 and MDM2 in Low-grade Osteosarcoma: A Genetic Study of 22 Cases With Clinicopathologic Analysis.He X et al
10327672322020Genomics and the Immune Landscape of Osteosarcoma.Wu CC et al
11253198672014Translational biology of osteosarcoma.Kansara M et al
12327672312020Genomic Complexity of Osteosarcoma and Its Implication for Preclinical and Clinical Targeted Therapies.Schott C et al
13266322672015Exome sequencing of osteosarcoma reveals mutation signatures reminiscent of BRCA deficiency.Kovac M et al
14277603072017Molecular genetics of osteosarcoma.Rickel K et al
15286437812017Recurrent mutation of IGF signalling genes and distinct patterns of genomic rearrangement in osteosarcoma.Behjati S et al
16296684992018Tumor Syndromes Predisposing to Osteosarcoma.Hameed M et al
17103938371999Hibernomas are characterized by homozygous deletions in the multiple endocrine neoplasia type I region. Metaphase fluorescence in situ hybridization reveals complex rearrangements not detected by conventional cytogenetics.Gisselsson D et al
18167303252006Elucidating the mechanisms of coupled electron transfer and catalytic reactions by protein film voltammetry.Hirst J et al
19201961712010Characterization of the 12q15 MDM2 and 12q13-14 CDK4 amplicons and clinical correlations in osteosarcoma.Mejia-Guerrero S et al
20124023052002Genetic imbalances revealed by comparative genomic hybridization in osteosarcomas.Ozaki T et al
21276153222016Mutational signatures of ionizing radiation in second malignancies.Behjati S et al

External Links


Judith VMG Bovée ; Paola Dal Cin

Osteogenic tumors

Atlas Genet Cytogenet Oncol Haematol. 2022-03-04

Online version: http://atlasgeneticsoncology.org/solid-tumor/208933/osteogenic-tumors