The diagnostic utility of DNA copy number analysis of core needle biopsies from soft tissue and bone tumors

Morphologic and immunohistochemical analysis of preoperative core needle biopsies (CNB) is important in the management of patients with soft tissue and bone tumors (STBTs). Most SBTB subtypes have more or less extensive DNA copy number aberrations (CNA), potentially providing useful diagnostic information. To evaluate the technical feasibility of single nucleotide polymorphism (SNP) array analysis and the diagnostic usefulness of the copy number profiles, we studied CNBs from 171 patients with suspected STBTs. SNP array analysis could be performed on 168 (98%) of the samples. The CNA profile was compatible with the CNB diagnosis in 87% of the cases. Discrepant cases were dominated by false-negative results due to nonrepresentative material or contamination with normal cells. 70 genomic profiles were indicative of specific histopathologic tumor entities and in agreement with the corresponding CNB diagnoses in 83%. In 96 of the cases with aberrant CNA profiles, the SNP profiles were of sufficient quality for segmentation, allowing clustering analysis on the basis of the Jaccard similarity index. The analysis of these segment files showed three major CNA clusters, based on the complexity levels and the predominance of gains versus losses. For 43 of these CNB samples, we had SNP array data also from their corresponding surgical samples. In 33 of these pairs, the two corresponding samples clustered next to each other, with Jaccard scores ranging from 0.61 to 0.99 (median 0.96). Also, for those tumor pairs that did not cluster together, the Jaccard scores were relatively high (median 0.9). 10 cases showed discrepant results, mainly due to varying degrees of normal cell contamination or technical issues. Thus, the copy number profile seen in a CNB is typically highly representative of the major cell population in the tumor.

Automated summary

Morphologic and immunohistochemical analysis of preoperative core needle biopsies is crucial for the management of soft tissue and bone tumors. The use of single nucleotide polymorphism array analysis can provide diagnostic information about copy number aberrations.