Ring chromosomes and low-grade gene amplification in an atypical lipomatous tumor with minimal nuclear atypia.
Atypical lipomatous tumors (ALTs) are characterized by supernumerary ring chromosomes and/or giant marker chromosomes, which typically are composed of interspersed, amplified 12q-sequences, are C-band negative, lack alpha-satellite sequences, and display high copy numbers of several oncogenes, including HMGA2 (a.k.a. HMGIC) and MDM2, from the 12q13-15 region. In the present study, we report the cytogenetic and molecular genetic findings in an ALT with minimal nuclear atypia from a 16-year-old boy. At G-banding analysis, 1-3 supernumerary ring chromosomes were detected. Combined binary ratio labeling fluorescence in situ hybridization (COBRA-FISH) showed that the rings were entirely composed of material from chromosome 12, and by further FISH analysis with locus-specific probes it was revealed that they consisted of two tandemly arranged copies of the segment 12p11.2-p13.2 to 12q21.2-q23.1. Within that segment of chromosome 12, there was a small deletion including the HMGA2 locus. There was no variation in ring size and no interphase bridges could be detected, indicating that the ring chromosomes were mitotically relatively stable. The present case thus adds support to the concept that there exists a subset of ALT with limited or minimal nuclear atypia and low-level amplification of 12q sequences, further suggesting the possibility of a molecular genetic continuum between lipoma and classical examples of ALT. Furthermore, the present data strongly imply that it is the composition of the rings rather than the ring chromosome formation as such that causes the genetic instability and nuclear atypia frequently seen in ALTs.
Storlazzi
Clelia Tiziana
CT
Department of Clinical Genetics, Lund University Hospital, 221 85 Lund, Sweden. tizianast@hotmail.com
Mertens
Fredrik
F
Domanski
Henryk
H
Fletcher
Christopher D M
CD
Wiegant
Joop
J
Mandahl
Nils
N
D000293:Adolescent; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000378:metabolism / Q000473:pathology; D002871:Chromosome Banding; D002881:Chromosomes, Human, Pair 12; D003094:Collagen / Q000378:metabolism; D025743:HMGA2 Protein / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D008297:Male; D008938:Mitosis; D018205:Neoplasms, Adipose Tissue / Q000235:genetics*; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins / Q000235:genetics; D051736:Proto-Oncogene Proteins c-mdm2; D012303:Ring Chromosomes; D012983:Soft Tissue Neoplasms / Q000235:genetics* / Q000473:pathology
D025743:HMGA2 Protein; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D003094:Collagen; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2