Loss of heterozygosity at 12q14-15 often occurs in stage I soft tissue sarcomas and is associated with MDM2 amplification in tumors at various stages.
Few studies have investigated the loss of heterozygosity and microsatellite instability in soft tissue sarcomas. Therefore, we analyzed samples of human soft tissue sarcomas to determine the status of the chromosomal region 12q14-15, which contains the MDM2 gene encoding the well-known counterpart of the tumor suppressor p53. In addition, we determined whether an amplified MDM2 gene was present in the samples. Of the 88 soft tissue sarcoma samples, 24 (27%) showed evidence of loss of heterozygosity of markers representing 12q14-15, and 12 (14%) showed evidence of microsatellite instability. Of the 72 samples analyzed by semiquantitative polymerase chain reaction, 15 (21%) possessed an amplified MDM2 gene. Loss of heterozygosity (P =.008) and microsatellite instability (P =.035) were significantly more common in Stage I tumors than in higher stage tumors. This result indicated that these alterations occur early in soft tissue sarcoma progression and possibly define a subgroup of soft tissue sarcoma. Surprisingly, MDM2 amplification in soft tissue sarcoma patients was associated with a prognosis better than that of patients without the amplification; however, this difference was not statistically significant (P =.6). Furthermore, of the tumors with an MDM2 amplification, 40% (6/15) also experienced loss of heterozygosity at 12q14-15; in contrast, only 16% of tumors without an MDM2 amplification (9/57) underwent a loss of heterozygosity. A concomitant occurrence of deletions and amplifications resulting from deficiencies in the nonhomologous end-joining pathway could in part explain this finding.
Taubert
Helge
H
Institute of Pathology, Martin Luther University Halle-Wittenberg, Halle, Germany. helge.taubert@medizin.uni-halle.de
Schuster
Katja
K
Brinck
Ulrich
U
Bartel
Frank
F
Kappler
Matthias
M
Lautenschläger
Christine
C
Bache
Matthias
M
Trump
Cornelia
C
Schmidt
Hannelore
H
Holzhausen
Hans-Jürgen
HJ
Würl
Peter
P
Schlott
Thilo
T
D002881:Chromosomes, Human, Pair 12 / Q000235:genetics*; D005260:Female; D005784:Gene Amplification; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051736:Proto-Oncogene Proteins c-mdm2; D012509:Sarcoma / Q000235:genetics* / Q000473:pathology*
D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2