Cytogenetic intratumor heterogeneity in soft tissue tumors

Abstract Multiple (two to seven) samples, obtained from the same surgical specimen or at different occasions, were analyzed in 54 benign and malignant soft tissue tumors, to investigate cytogenetic clonal evolution. In 28 tumors only normal karyotypes were found. Ten tumors had abnormal karyotypes, but were noninformative, most often due to a high level of karyotypic complexity or great cell-to-cell variation. Sixteen tumors were informative: four (leiomyosarcoma, liposarcoma, malignant Schwannoma, and a benign mesenchymal tumor, probably leiomyoma) had identical karyotypes in different samples, whereas the remaining 12 tumors (seven malignant fibrous histiocytomas [MFH], two leiomyosarcomas, two liposarcomas, and one synovial sarcoma) displayed intersample heterogeneity. Also, intrasample heterogeneity was detected; more than one clone was found in 21 of 73 samples with aberrations from 26 tumors. The different clones were related in all cases except two. In seven cases, samples from different occasions were studied, and clonal evolution could be evidenced in five of them, whereas in two cases the karyotypes remained unchanged. The results indicate that the acquisition of ring chromosomes is an early event in the development of MFH and possibly also pleomorphic liposarcoma. The findings, together with previous data, also indicate that rearrangements of 19p13 are late events in the progression of pleomorphic sarcomas. The overall conclusion from this study is that cytogenetic heterogeneity is common in soft tissue tumors, and that this might influence the evaluation of cytogenetic and molecular genetic findings.