TY - JOUR
T1 - MDM2 amplification in rod-shaped chromosomes provides clues to early stages of circularized gene amplification in liposarcoma
AU - Sydow, Saskia
AU - Piccinelli, Paul
AU - Mitra, Shamik
AU - Tsagkozis, Panagiotis
AU - Hesla, Asle
AU - B. R. De Mattos, Camila
AU - Köster, Jan
AU - Magnusson, Linda
AU - Nilsson, Jenny
AU - Ameur, Adam
AU - Wardenaar, René
AU - Foijer, Floris
AU - Spierings, Diana
AU - Mertens, Fredrik
PY - 2024/12
Y1 - 2024/12
N2 - Well-differentiated liposarcoma (WDLS) displays amplification of genes on chromosome 12 (Chr12) in supernumerary ring or giant marker chromosomes. These structures have been suggested to develop through chromothripsis, followed by circularization and breakage-fusion-bridge (BFB) cycles. To test this hypothesis, we compared WDLSs with Chr12 amplification in rod-shaped chromosomes with WDLSs with rings. Both types of amplicons share the same spectrum of structural variants (SVs), show higher SV frequencies in Chr12 than in co-amplified segments, have SVs that fuse the telomeric ends of co-amplified chromosomes, and lack interspersed deletions. Combined with the finding of cells with transient rod-shaped structures in tumors with ring chromosomes, this suggests a stepwise process starting with the gain of Chr12 material that, after remodeling which does not fit with classical chromothripsis, forms a dicentric structure with other chromosomes. Depending on if and when telomeres from other chromosomes are captured, circularized or linear gain of 12q sequences will predominate.
AB - Well-differentiated liposarcoma (WDLS) displays amplification of genes on chromosome 12 (Chr12) in supernumerary ring or giant marker chromosomes. These structures have been suggested to develop through chromothripsis, followed by circularization and breakage-fusion-bridge (BFB) cycles. To test this hypothesis, we compared WDLSs with Chr12 amplification in rod-shaped chromosomes with WDLSs with rings. Both types of amplicons share the same spectrum of structural variants (SVs), show higher SV frequencies in Chr12 than in co-amplified segments, have SVs that fuse the telomeric ends of co-amplified chromosomes, and lack interspersed deletions. Combined with the finding of cells with transient rod-shaped structures in tumors with ring chromosomes, this suggests a stepwise process starting with the gain of Chr12 material that, after remodeling which does not fit with classical chromothripsis, forms a dicentric structure with other chromosomes. Depending on if and when telomeres from other chromosomes are captured, circularized or linear gain of 12q sequences will predominate.
U2 - 10.1038/s42003-024-06307-1
DO - 10.1038/s42003-024-06307-1
M3 - Article
C2 - 38769442
AN - SCOPUS:85193712817
SN - 2399-3642
VL - 7
JO - Communications Biology
JF - Communications Biology
IS - 1
M1 - 606
ER -