MDM2 Amplification in Rod-shaped Chromosomes Provides Clues to Early Stages of Circularized Gene Amplification in Liposarcoma

Overview

Journal Commun Biol

Specialty Biology

Date 2024 May 20

PMID 38769442

Authors

Saskia Sydow

Paul Piccinelli

Shamik Mitra

Panagiotis Tsagkozis

Asle Hesla

Camila B R De Mattos

Jan Koster

Linda Magnusson

Jenny Nilsson

Adam Ameur

Rene Wardenaar

Floris Foijer

Diana Spierings

Fredrik Mertens

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

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PMID: 39322633 PMC: 11424644. DOI: 10.1038/s41525-024-00430-y.

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