Chromosome aberrations and HEY1-NCOA2 fusion gene in a mesenchymal chondrosarcoma.
Mesenchymal chondrosarcomas are fast-growing tumors that account for 2-10% of primary chondrosarcomas. Cytogenetic information is restricted to 12 cases that did not show a specific aberration pattern. Recently, two fusion genes were described in mesenchymal chondrosarcomas: a recurrent HEY1-NCOA2 found in tumors that had not been cytogenetically characterized and an IRF2BP2-CDX1 found in a tumor carrying a t(1;5)(q42;q32) translocation as the sole chromosomal abnormality. Here, we present the cytogenetic and molecular genetic analysis of a mesenchymal chondrosarcoma in which the patient had two histologically indistinguishable tumor lesions, one in the neck and one in the thigh. An abnormal clone with the G-banding karyotype 46,XX,add(6)(q23),add(8)(p23),del(10)(p11),+12,-15[6] was found in the neck tumor whereas a normal karyotype, 46,XX, was found in the tumor of the thigh. RT-PCR and Sanger sequencing showed that exon 4 of HEY1 was fused to exon 13 of NCOA2 in the sample from the thigh lesion; we did not have spare material to perform a similar analysis of the neck tumor. Examining the published karyotypes we observed numerical or structural aberrations of chromosome 8 in the majority of the karyotyped mesenchymal chondrosarcomas. Chromosome 8 was also structurally affected in the present study. The pathogenetic mechanisms behind this nonrandom involvement are unknown, but the presence on 8q of two genes, HEY1 and NCOA2, now known to be involved in mesenchymal chondrosarcoma tumorigenesis is, of course, suggestive.
Section for Cancer Cytogenetics, Institute for Cancer Genetics and Informatics, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
Ioannis
I
Panagopoulos
Section for Cancer Cytogenetics, Institute for Cancer Genetics and Informatics, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
Ludmila
L
Gorunova
Department of Pathology, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
Bodil
B
Bjerkehagen
Department of Oncology, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
Kjetil
K
Boye
Section for Cancer Cytogenetics, Institute for Cancer Genetics and Informatics, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
Sverre
S
Heim
D000328:Adult; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D001859:Bone Neoplasms / Q000235:genetics* / Q000473:pathology; D018797:Cell Cycle Proteins / Q000235:genetics*; D018211:Chondrosarcoma, Mesenchymal / Q000235:genetics* / Q000473:pathology; D002869:Chromosome Aberrations; D002898:Chromosomes, Human, Pair 8; D005091:Exons; D005260:Female; D005269:Femur / Q000473:pathology; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000473:pathology; D006801:Humans; D059785:Karyotype; D051958:Nuclear Receptor Coactivator 2 / Q000235:genetics*; D015514:Oncogene Proteins, Fusion; D011993:Recombinant Fusion Proteins / Q000235:genetics; D014407:Tumor Cells, Cultured
D051792:Basic Helix-Loop-Helix Proteins; D018797:Cell Cycle Proteins; D051958:Nuclear Receptor Coactivator 2; D015514:Oncogene Proteins, Fusion; D011993:Recombinant Fusion Proteins; C485631:HEY1 protein, human; C498001:NCOA2 protein, human