Abstract
Purpose. Patients with soft tissue sarcomas (STS) are at increased risk of second primary malignancies, including a second STS, but distinction between metastases and a second primary STS is difficult. Patients and Methods. Array-based comparative genomic hybridization (aCGH) was applied to 30 multiple STS of the extremities and the trunk wall from 13 patients. Different histotypes were present with malignant fibrous histiocytomas/undifferentiated pleomorphic sarcomas being the predominant subtype. Results. aCGH profiling revealed genetic complexity with multiple gains and losses in all tumors. In an unsupervised hierarchical cluster analysis, similar genomic profiles and close clustering between the first and subsequent STS were identified in 5 cases, suggesting metastatic disease, whereas the tumors from the remaining 8 patients did not cluster and showed only weak pairwise correlation, suggesting development of second primary STS. Discussion. The similarities and dissimilarities identified in the first and second STS suggest that genetic profiles can be used to distinguish soft tissue metastases from second primary STS. The demonstration of genetically different soft tissue sarcomas in the same patient suggests independent tumor origin and serves as a reminder to consider development of second primary STS, which has prognostic and therapeutic implications.
Highlights
The first observations of an increased risk of secondary sarcoma development came from individuals treated for childhood cancers such as retinoblastoma, leukemia, Wilms’ tumor, Hodgkin’s lymphoma, and sarcoma [1,2,3,4,5,6,7,8,9,10,11,12,13]
Unsupervised hierarchical cluster analysis, based on the ∼ 27 000 clones that survived the filters in BioArray Software Environment (BASE), revealed close clustering of the tumors from five individuals without significant differences between the first and subsequent soft tissue sarcoma (STS) (43% and 41% of the genome altered) (Figure 1 and Table 1, cases 1, 2, 6, 9, and 12)
Despite multidisciplinary and multimodality treatment, distant metastases develop in about 30% of STS patients
Summary
The first observations of an increased risk of secondary sarcoma development came from individuals treated for childhood cancers such as retinoblastoma, leukemia, Wilms’ tumor, Hodgkin’s lymphoma, and sarcoma [1,2,3,4,5,6,7,8,9,10,11,12,13]. After exclusion of STS in neurofibromatosis patients and STS that developed in irradiated fields, an increased risk of a second primary STS remains [17]. Metachronous STS has been described in 1% of sarcoma patients [16, 17, 20] and this observation constitutes the basis for our study on similarities/differences in the genetic profiles of tumors from patients with multiple STS. We applied array-based comparative genomic hybridization (aCGH) that utilizes BAC clones with tiling coverage of the whole genome and allows detailed copy-number analysis, to a series of 30 metachronous STS of different histopathological subtypes from 13 patients
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