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bioRxiv · 10.1101/2024.06.18.599481

Loss of chromosome cytoband 13q14.2 orchestrates breast cancer pathogenesis and drug response

Shahrouzi, P.·Azimzade, Y.·Brankiewicz, W.·Bhatia, S.·Kunke, D.·Richard, D.·Tekpli, X.·Kristensen, V. N.·Duijf, P. H. G.
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Abstract

Breast cancer (BCa) is a major global health challenge, characterized by chromosomal instability (CIN) and subsequent acquisition of extensive somatic copy number alterations (CNAs). CNAs including amplifications and deletions, significantly influence intra-tumor heterogeneity and the tumor microenvironment (TME). Among these, the loss of chromosome 13q14.2 emerges as a considerable factor in BCa pathogenesis and treatment responses. We provide evidence that this genomic alteration is under positive selective pressure, correlating with poorer patient survival. Furthermore, through multi-omic and in vitro analyses, we uncover a dual role of 13q14.2 loss: it confers a survival advantage to tumor cells and modulate the cell cycle and pro-apoptotic pathways in cancer cells, affecting macrophages population in the TME, while paradoxically increasing tumor susceptibility to BCL2 inhibitors. These findings suggest that targeting 13q14.2 as a biomarker in BCa could enhance the efficacy of existing treatments and offer a new avenue for improving clinical outcomes in BCa. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/599481v1_fig1.gif" ALT="Figure 1"> View larger version (93K): org.highwire.dtl.DTLVardef@123f961org.highwire.dtl.DTLVardef@c952f0org.highwire.dtl.DTLVardef@16430eborg.highwire.dtl.DTLVardef@c7c954_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOFigure 1.C_FLOATNO Graphical abstract C_FIG

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Shahrouzi, P., Azimzade, Y., Brankiewicz, W., Bhatia, S., Kunke, D., Richard, D., Tekpli, X., Kristensen, V. N., Duijf, P. H. G.. 2024-06-20. Loss of chromosome cytoband 13q14.2 orchestrates breast cancer pathogenesis and drug response. https://doi.org/10.1101/2024.06.18.599481

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