title: 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.
abstract: 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.
authors: Institute of Pathology, Martin Luther University Halle-Wittenberg, Halle, Germany. helge.taubert@medizin.uni-halle.de
authors: Helge
authors: H
authors: Taubert
authors: Katja
authors: K
authors: Schuster
authors: Ulrich
authors: U
authors: Brinck
authors: Frank
authors: F
authors: Bartel
authors: Matthias
authors: M
authors: Kappler
authors: Christine
authors: C
authors: Lautenschläger
authors: Matthias
authors: M
authors: Bache
authors: Cornelia
authors: C
authors: Trump
authors: Hannelore
authors: H
authors: Schmidt
authors: Hans-Jürgen
authors: HJ
authors: Holzhausen
authors: Peter
authors: P
authors: Würl
authors: Thilo
authors: T
authors: Schlott
mesh_terms: 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*
chemical_list: D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2