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Research: Loss of multilevel 3D genome organization during breast cancer progression
- Roberto Rossini,
- Saleh Oshaghi,
- Maxim Nekrasov,
- Aurélie Bellanger,
- Renae Domaschenz,
- Yasmin Dijkwel,
- Mohamed Abdelhalim,
- Rahul Agrawal,
- Marit Ledsaak,
- Philippe Collas,
- Ragnhild Eskeland,
- David Tremethick,
- and Jonas Paulsen
Genome Res. January 2026 36: 20-37; Published in Advance October 9, 2025, doi:10.1101/gr.280791.125
...a normal to a breast cancer malignant state remains unknown. To address this, we have conducted an analysis combining Hi-C data with lamina-associated domains (LADs), epigenomic marks, and gene expression in an in vitro model of breast cancer progression. Our results reveal that although the fundamental...
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Research: Analysis of canine gene constraint identifies new variants for orofacial clefts and stature
- Reuben M. Buckley,
- Nüket Bilgen,
- Alexander C. Harris,
- Peter Savolainen,
- Cafer Tepeli,
- Metin Erdoğan,
- Aitor Serres Armero,
- Dayna L. Dreger,
- Frank G. van Steenbeek,
- Marjo K. Hytönen,
- Heidi G. Parker,
- Jessica Hale,
- Hannes Lohi,
- Bengi Çınar Kul,
- Adam R. Boyko,
- and Elaine A. Ostrander
Genome Res. May 2025 35: 1080-1093; Published in Advance March 24, 2025, doi:10.1101/gr.280092.124
...trait. We characterize coding variation across 2291 canine s from over 200 phylogenetically informed breeds/subpopulations and develop a canine-specific mutation model to determine whether gene/site constraint metrics are predictive of variant fitness consequences. From this, we identify breed...
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Research: Alternative splicing generates HER2 isoform diversity underlying antibody–drug conjugate resistance in breast cancer
- Gabriela D.A. Guardia,
- Carlos H. dos Anjos,
- Aline Rangel-Pozzo,
- Filipe F. dos Santos,
- Alexander Birbrair,
- Paula F. Asprino,
- Anamaria A. Camargo,
- and Pedro A.F. Galante
Genome Res. September 2025 35: 1942-1958; Published in Advance July 15, 2025, doi:10.1101/gr.280304.124
..., promoting tumor cell proliferation and survival (Yarden and Sliwkowski 2001). The HER2-positive breast cancer subtype is associated with aggressive tumor behavior and poor prognosis in the absence of anti-HER2-targeted therapy (Slamon et al. 1987).The advent of HER2-targeted therapies has significantly...
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Research: Loss of epigenetic suppression of retrotransposons with oncogenic potential in aging mammary luminal epithelial cells
- Parijat Senapati,
- Masaru Miyano,
- Rosalyn W. Sayaman,
- Mudaser Basam,
- Amy Leung,
- Mark A. LaBarge,
- and Dustin E. Schones
Genome Res. August 2023 33: 1229-1241; Published in Advance July 18, 2023, doi:10.1101/gr.277511.122
...on TE silencing and the functional consequences of this have remained unclear. To assess the epigenetic regulation of TEs in aging, we profiled DNA methylation in human mammary luminal epithelial cells (LEps)—a key cell lineage implicated in age-related breast cancers—from younger and older women. We...
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Research: Estrogen receptor 1 chromatin profiling in human breast tumors reveals high inter-patient heterogeneity with enrichment of risk SNPs and enhancer activity at most-conserved regions
- Stacey E.P. Joosten,
- Sebastian Gregoricchio,
- Suzan Stelloo,
- Elif Yapıcı,
- Chia-Chi Flora Huang,
- Kerim Yavuz,
- Maria Donaldson Collier,
- Tunç Morova,
- Umut Berkay Altintaş,
- Yongsoo Kim,
- Sander Canisius,
- Cathy B. Moelans,
- Paul J. van Diest,
- Gozde Korkmaz,
- Nathan A. Lack,
- Michiel Vermeulen,
- Sabine C. Linn,
- and Wilbert Zwart
Genome Res. April 2024 34: 539-555; Published in Advance May 6, 2024, doi:10.1101/gr.278680.123
....zwart@nki.nlAbstractEstrogen Receptor 1 (ESR1; also known as ERα, encoded by ESR1 gene) is the main driver and prime drug target in luminal breast cancer. ESR1 chromatin binding is extensively studied in cell lines and a limited number of human tumors, using consensi of peaks shared among samples. However, little is known about inter-tumor...
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Research: Comprehensive functional annotation of ESR1-driven enhancers in breast cancer reveals hierarchical activity independent of genomic and epigenomic contexts
- Yanis Zekri,
- Sebastian Gregoricchio,
- Elif Yapıcı,
- Chia-Chi Flora Huang,
- Tunç Morova,
- Umut Berkay Altıntaş,
- Gozde Korkmaz,
- Nathan A. Lack,
- and Wilbert Zwart
Genome Res. July 2025 35: 1530-1543; Published in Advance June 10, 2025, doi:10.1101/gr.280320.124
.... These findings are confirmed by genomic data in situ, indicating that enhancer activation within a chromatinized context is robustly captured in a plasmid-based reporter assay. In silico integration of our findings with publicly available functional genomics data sets from breast cancer cell lines and tumor...
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Method: Modeling and predicting cancer clonal evolution with reinforcement learning
- Stefan Ivanovic and
- Mohammed El-Kebir
Genome Res. July 2023 33: 1078-1088; Published in Advance June 21, 2023, doi:10.1101/gr.277672.123
...@illinois.eduAbstractCancer results from an evolutionary process that typically yields multiple clones with varying sets of mutations within the same tumor. Accurately modeling this process is key to understanding and predicting cancer evolution. Here, we introduce clone to mutation (CloMu), a flexible and low-parameter tree...
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Resource: Multiscale network modeling reveals the gene regulatory landscape driving cancer prognosis in 32 cancer types
- Peng Xu and
- Bin Zhang
Genome Res. October 2023 33: 1806-1817; Published in Advance October 31, 2023, doi:10.1101/gr.278063.123
...Peng Xu1,2,3 and Bin Zhang1,2,3,4 1Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA; 2Mount Sinai Center for Transformative Disease Modeling, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA; 3Icahn Institute...
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Method: Genome-wide cancer-specific chromatin accessibility patterns derived from archival processed xenograft tumors
- Shelsa S. Marcel,
- Austin L. Quimby,
- Melodie P. Noel,
- Oscar C. Jaimes,
- Marjan Mehrab-Mohseni,
- Suud A. Ashur,
- Brian Velasco,
- James K. Tsuruta,
- Sandeep K. Kasoji,
- Charlene M. Santos,
- Paul A. Dayton,
- Joel S. Parker,
- Ian J. Davis,
- and Samantha G. Pattenden
Genome Res. December 2021 31: 2327-2339; Published in Advance November 23, 2021, doi:10.1101/gr.275219.121
...cell renal cell carcinoma (ccRCC) tumors (P = 0.011) (Fig. 3A), EWS894 Ewing sarcoma tumors (P = 0.044) (Fig. 3B), and MDA-MB-231 basal breast tumors (P = 0.008) (Fig. 3C).View larger version: In this window In a new window Figure 3. Nanodroplets facilitate the extraction of chromatin from archival...
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Research: SMARCA4 regulates gene expression and higher-order chromatin structure in proliferating mammary epithelial cells
- A. Rasim Barutcu,
- Bryan R. Lajoie,
- Andrew J. Fritz,
- Rachel P. McCord,
- Jeffrey A. Nickerson,
- Andre J. van Wijnen,
- Jane B. Lian,
- Janet L. Stein,
- Job Dekker,
- Gary S. Stein,
- and Anthony N. Imbalzano
Genome Res. September 2016 26: 1188-1201; Published in Advance July 19, 2016, doi:10.1101/gr.201624.115
...questioned (Thompson et al. 2015). On the other hand, SMARCA4 is essential, as SMARCA4 mice are embryonic lethal, and SMARCA4 heterozygous mice show developmental defects and are prone to mammary tumor formation (Bultman et al. 2000, 2008). SMARCA4 has been shown to be involved in many developmental...

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