Radiation-associated sarcomas are characterized by complex karyotypes withfrequent rearrangements of chromosome arm 3p

Ionizing radiation is a well-known risk factor for sarcoma development. To investigate whether radiation-associated sarcomas are characterized by chro mosome aberrations that distinguish them from de novo sarcomas, we identifi ed those patients in our series of more than 500 cytogenetically abnormal s arcomas that fulfilled the following criteria: (1) each patient should have been irradiated for another malignancy at least 3 years prior to the sarco ma diagnosis, and (2) the sarcoma should have developed within the field of radiation. Ten patients fulfilling these criteria could be retrieved (medi an age at sarcoma diagnosis was 55 years, range 17-79; median latency perio d between primary tumor and radiation-associated sarcoma was 9 years, range 4-30). The diagnoses were typical for radiation-associated sarcomas: 2 eac h of malignant fibrous histiocytoma, leiomyosarcoma, and pleomorphic sarcom a, and 1 each of osteosarcoma, fibrosarcoma, myxofibrosarcoma, and spindle cell sarcoma. All 10 cases had relatively complex karyotypes with multiple, mostly unbalanced, structural rearrangements, similar to what has been rep orted in de novo sarcomas of the corresponding histologic subtypes. The onl y cytogenetic features that were un usually frequent among the radiation-as sociated sarcomas were the finding of unrelated clones in 3 cases, and loss of material from chromosome arm 3p, in particular 3p21-3pter, in 8 cases. Loss of the same chromosome segment has been described in 4 of the 8 previo usly published cases of radiation-associated sarcomas that have been analyz ed after short-term culturing, which makes this imbalance significantly (P < 0.001) more frequent among radiation-associated sarcomas (22 of 18 cases) than among unselected cases of the corresponding histologic subtypes (74 o f 282 cases). In contrast to the cytogenetic results, no 3p deletions were detected among the 6 cases of the present series that could be analyzed by comparative,genomic hybridization (CGH). The most frequent imbalance detect ed by CGH was gain of 15cen-q15 (3 cases), followed by loss of chromosome 1 3 and gain of 5p, and 7cen-q22, each detected in 2 cases. (C) Elsevier Scie nce Inc., 1999. All rights reserved.