Recurrent gains of 1q, 8 and 12 in the Ewing family of tumours by comparative genomic hybridization

Abstract

Summary Comparative genomic hybridization (CGH) was used to detect copy number changes of DNA sequences in the Ewing family of tumours (ET). We analysed 20 samples from 17 patients. Fifteen tumours (75%) showed copy number changes. Gains of DNA sequences were much more frequent than losses, the majority of the gains affecting whole chromosomes or whole chromosome arms. Recurrent findings included copy number increases for chromosomes 8 (seven out of 20 samples; 35%), 1q (five samples; 25%) and 12 (five samples; 25%). The minimal common regions of these gains were the whole chromosomes 8 and 12, and 1q21-22. High-level amplifications affected 8q13-24, 1q and 1q21-22, each once. Southern blot analysis of the specimen with high-level amplification at 1q21-22 showed an amplification of FLG and SPRR3, both mapped to this region. All cases with a gain of chromosome 12 simultaneously showed a gain of chromosome 8. Comparison of CGH findings with cytogenetic analysis of the same tumours and previous cytogenetic reports of ET showed, in general, concordant results. In conclusion, our findings confirm that secondary changes, which may have prognostic significance in ET, are trisomy 8, trisomy 12 and a gain of DNA sequences in 1 q.

Do DNA copy number changes differentiate uterine from non-uterine leiomyosarcomas and predict metastasis?

“…Increased sequence copy number at 1q21.q23 has been detected frequently in several malignancies (see Knuutila et al 50 and references therein), but especially in sarcomas, including leiomyosarcoma, liposarcoma, osteosarcoma, chondrosarcoma, and malignant fibrous histiocytoma. 21,24,26,27,34,44,[51][52][53][54][55][56] This region harbors several genes of potential significance. [56][57][58] Our study showed gains and high-level amplifications in 17p in approximately 40% of the cases.…”

Array CGH and gene-expression profiling reveals distinct genomic instability patterns associated with DNA repair and cell-cycle checkpoint pathways in Ewing's sarcoma

“…The most common correspond to trisomies of chromosome 8 (Mugneret et al, 1988), 12 and gain of DNA sequences in 1q (Armengol et al, 1997). The relation between these secondary changes and clinical outcome is quite controversial.…”

Prognostic impact of chromosomal aberrations in Ewing tumours

“…Recently, deletions of INK4A (9p21) and TP53 alterations (17p13) appeared to define small groups of patients with markedly poor outcome (Kovar et al, 1997;de Alava et al, 2000;Wei et al, 2000). Besides molecular genetic markers of possible prognostic value, increased copy number of chromosomes 8, 12, and of 1q and loss of 1p have been discussed to be associated with an advanced stage of disease, but with conflicting evidence as to whether they are associated with a poor clinical outcome (Douglass et al, 1990;Armengol et al, 1997;Maurici et al, 1998;Hattinger et al, 1999;Kullendorff et al, 1999;Tarkkanen et al, 1999). As ETs are rare all these previous studies were performed on small numbers of patients and could not reach firm conclusions with regard to the prognostic impact of the additional genetic aberrations.…”

“…Additional structural aberrations are less common than numerical changes, although unbalanced rearrangements involving chromosomes 1 and 16 are quite frequently seen. In the majority of these cases the net imbalance is gain of 1q with simultaneous loss of 16q (Mugneret et al, 1988;Douglass et al, 1990;Hattinger et al, 1996;Armengol et al, 1997;Stark et al, 1997;Kullendorff et al, 1999;Tarkkanen et al, 1999).…”