Gains of 12q are the most frequent genomic imbalances in adult fibrosarcoma and are correlated with a poor outcome.
Comparative genomic hybridization was used to analyze 41 adult fibrosarcomas from 34 patients. Thirty-one patients showed in their tumors DNA sequence copy number changes (mean 11, range 3-25). The minimal common regions for the most frequent gains were narrowed down to 12q21 (18 cases); 12q14-q15 and 14q22 (16 cases each); 4q22, 7q31, and 14q23-q24 (15 cases each); and 4q21, 4q23-q24, 8q22, and 12q22 (14 cases each). Twenty-five high-level amplifications were observed in 12 samples. 12q21 and 18p were affected three times each; and 1p21, 4q31.3, 7p21, 12q14-q15, Xp22.1-p22.2, and Xq22-q23 two times each. Losses were less frequent than gains. Early stages of adult fibrosarcomas were characterized by frequent gains of chromosomes 2, 4q, and 14q, whereas gains of chromosomes 7 and 8q were associated with progression. Gains of 12q were frequent in all of the developmental steps of this soft-tissue sarcoma. By investigation of several tumors of the same patient, a number of corresponding changes were always detected. Adult fibrosarcomas from patients who died during the observation time showed statistically significant more frequent gains of 8q, 12q, 13q, and 15q compared to the fibrosarcomas of patients who are alive. Gains and high-level amplifications of 12q14-q22, which were the most frequent genomic imbalances, partly reflected an MDM2 amplification, indicating the importance of this region in the tumorigenesis of sarcomas. In adult fibrosarcomas, a gain of 12q22 correlated significantly (P = 0.028) with a poor overall survival rate.
Schmidt
H
H
Institute of Pathology, Martin Luther University Halle-Wittenberg, Halle, Germany. hannelore.schmidt@medizin.uni-halle.de
Taubert
H
H
Würl
P
P
Kappler
M
M
Lange
H
H
Bartel
F
F
Bache
M
M
Holzhausen
H-J
HJ
Hinze
R
R
D000008:Abdominal Neoplasms / Q000235:genetics / Q000401:mortality / Q000556:secondary; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D022981:Allelic Imbalance / Q000235:genetics*; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics*; D005121:Extremities; D005260:Female; D005354:Fibrosarcoma / Q000235:genetics* / Q000401:mortality / Q000556:secondary; D005784:Gene Amplification / Q000235:genetics; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000401:mortality / Q000556:secondary; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins / Q000235:genetics; D051736:Proto-Oncogene Proteins c-mdm2; D015996:Survival Rate; D013899:Thoracic Neoplasms / Q000235:genetics / Q000401:mortality / Q000556:secondary
D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2