{"entity": "researcher", "timestamp": "2026-08-20T21:02:53.271Z", "family": "Lu", "given": "Wei-Ting", "initials": "WT", "orcid": "0000-0002-1405-4806", "affiliations": ["The Francis Crick Institute, London, UK. wei-ting.lu@crick.ac.uk."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/8acbe8b1a0394c668ccf21845b0b673e.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/8acbe8b1a0394c668ccf21845b0b673e"}}, "publications": [{"entity": "publication", "iuid": "44fe0e30267a4c5bb9ef485f98304fc4", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/44fe0e30267a4c5bb9ef485f98304fc4.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/44fe0e30267a4c5bb9ef485f98304fc4"}}, "title": "TRACERx analysis identifies a role for FAT1 in regulating chromosomal instability and whole-genome doubling via Hippo signalling.", "authors": [{"family": "Lu", "given": "Wei-Ting", "initials": "WT", "orcid": "0000-0002-1405-4806", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8acbe8b1a0394c668ccf21845b0b673e.json"}}, {"family": "Zalmas", "given": "Lykourgos-Panagiotis", "initials": "LP"}, {"family": "Bailey", "given": "Chris", "initials": "C", "orcid": "0000-0002-1602-8396", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/cb8c42a04f4a41b3ab7bda4562adce04.json"}}, {"family": "Black", "given": "James R M", "initials": "JRM", "orcid": "0000-0001-5598-7752", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/62cdf6c6e3d447c388119242d6801bdd.json"}}, {"family": "Martinez-Ruiz", "given": "Carlos", "initials": "C"}, {"family": "Pich", "given": "Oriol", "initials": "O", "orcid": "0000-0002-1956-1882", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f7234148c4574fa09a0054f8bb3284c5.json"}}, {"family": "Gimeno-Valiente", "given": "Francisco", "initials": "F"}, {"family": "Usaite", "given": "Ieva", "initials": "I"}, {"family": "Magness", "given": "Alastair", "initials": "A", "orcid": "0000-0001-9876-3863", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a1abf8dadf234750b4d2b565c753041a.json"}}, {"family": "Thol", "given": "Kerstin", "initials": "K"}, {"family": "Webber", "given": "Thomas A", "initials": "TA"}, {"family": "Jiang", "given": "Ming", "initials": "M", "orcid": "0009-0004-1794-366X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/dbbcef7099e9416cb6e779895943aa8b.json"}}, {"family": "Saunders", "given": "Rebecca E", "initials": "RE"}, {"family": "Liu", "given": "Yun-Hsin", "initials": "YH"}, {"family": "Biswas", "given": "Dhruva", "initials": "D"}, {"family": "Ige", "given": "Esther O", "initials": "EO", "orcid": "0009-0006-9227-8799", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/17be505f157f4dce8ae32f90eef920d2.json"}}, {"family": "Aerne", "given": "Birgit", "initials": "B"}, {"family": "Gr\u00f6nroos", "given": "Eva", "initials": "E", "orcid": "0000-0001-8303-5409", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1fa0868fdf094f1da9bd53d4ea2b0b5d.json"}}, {"family": "Venkatesan", "given": "Subramanian", "initials": "S", "orcid": "0000-0001-6454-8508", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ecacc5d56e504429823daac1d5ea2aeb.json"}}, {"family": "Stavrou", "given": "Georgia", "initials": "G", "orcid": "0000-0002-8427-5233", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d36e7adf2e0b4c40bda787373019b76e.json"}}, {"family": "Karasaki", "given": "Takahiro", "initials": "T"}, {"family": "Al Bakir", "given": "Maise", "initials": "M"}, {"family": "Renshaw", "given": "Matthew", "initials": "M", "orcid": "0000-0001-5238-9191", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/68b1c3e8effb4422aa2ae000d142a92f.json"}}, {"family": "Xu", "given": "Hang", "initials": "H", "orcid": "0000-0002-5847-655X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/802e8041166d495d928231c8c38203ed.json"}}, {"family": "Schneider-Luftman", "given": "Deborah", "initials": "D", "orcid": "0000-0001-5821-2135", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/14ea00edc1b543fb9f996bc11ae2d90d.json"}}, {"family": "Sharma", "given": "Natasha", "initials": "N"}, {"family": "Tovini", "given": "Laura", "initials": "L", "orcid": "0000-0002-4548-2811", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4ada258c28454f2f89b39c7d6d6433c0.json"}}, {"family": "TRACERx Consortium", "given": "", "initials": ""}, {"family": "Jamal-Hanjani", "given": "Mariam", "initials": "M"}, {"family": "McClelland", "given": "Sarah E", "initials": "SE", "orcid": "0000-0002-9987-4511", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c79544a14cdc4df480eb0f5b3e9a8fc2.json"}}, {"family": "Litchfield", "given": "Kevin", "initials": "K"}, {"family": "Birkbak", "given": "Nicolai J", "initials": "NJ", "orcid": "0000-0003-1613-9587", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/661a4f788ca449ddbb5d1eba7c709b6f.json"}}, {"family": "Howell", "given": "Michael", "initials": "M", "orcid": "0000-0003-0912-0079", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/111f5b9b742640e5b51e15b8b0873a95.json"}}, {"family": "Tapon", "given": "Nicolas", "initials": "N", "orcid": "0000-0001-5267-6510", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1147bd855b0c4fd09265fc7fad72370c.json"}}, {"family": "Fugger", "given": "Kasper", "initials": "K", "orcid": "0000-0001-9811-3983", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/03ad24ff24ca485aba3d89b0ce834b01.json"}}, {"family": "McGranahan", "given": "Nicholas", "initials": "N"}, {"family": "Bartek", "given": "Jiri", "initials": "J", "orcid": "0000-0003-2013-7525", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/288939950c0c4c6393d35c84e5128b5f.json"}}, {"family": "Kanu", "given": "Nnennaya", "initials": "N", "orcid": "0000-0001-7232-1952", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/61d0ad7ad361417eb51ff430c25f4fac.json"}}, {"family": "Swanton", "given": "Charles", "initials": "C", "orcid": "0000-0002-4299-3018", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e624db9004da4812a607b34b20cea0e7.json"}}], "type": "journal article", "published": "2025-01-00", "journal": {"title": "Nat. Cell Biol.", "issn": "1476-4679", "volume": "27", "issue": "1", "pages": "154-168", "issn-l": "1465-7392"}, "abstract": "Chromosomal instability (CIN) is common in solid tumours and fuels evolutionary adaptation and poor prognosis by increasing intratumour heterogeneity. Systematic characterization of driver events in the TRACERx non-small-cell lung cancer (NSCLC) cohort identified that genetic alterations in six genes, including FAT1, result in homologous recombination (HR) repair deficiencies and CIN. Using orthogonal genetic and experimental approaches, we demonstrate that FAT1 alterations are positively selected before genome doubling and associated with HR deficiency. FAT1 ablation causes persistent replication stress, an elevated mitotic failure rate, nuclear deformation and elevated structural CIN, including chromosome translocations and radial chromosomes. FAT1 loss contributes to whole-genome doubling (a form of numerical CIN) through the dysregulation of YAP1. Co-depletion of YAP1 partially rescues numerical CIN caused by FAT1 loss but does not relieve HR deficiencies, nor structural CIN. Importantly, overexpression of constitutively active YAP15SA is sufficient to induce numerical CIN. Taken together, we show that FAT1 loss in NSCLC attenuates HR and exacerbates CIN through two distinct downstream mechanisms, leading to increased tumour heterogeneity.", "doi": "10.1038/s41556-024-01558-w", "pmid": "39738653", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC11735399"}, {"db": "pii", "key": "10.1038/s41556-024-01558-w"}], "notes": [], "created": "2026-08-20T08:55:03.177Z", "modified": "2026-08-20T08:55:04.278Z"}, {"entity": "publication", "iuid": "12a923d86f454f0da28ae57d3a170b0d", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/12a923d86f454f0da28ae57d3a170b0d.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/12a923d86f454f0da28ae57d3a170b0d"}}, "title": "Induction of APOBEC3 Exacerbates DNA Replication Stress and Chromosomal Instability in Early Breast and Lung Cancer Evolution.", "authors": [{"family": "Venkatesan", "given": "Subramanian", "initials": "S", "orcid": "0000-0001-6454-8508", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ecacc5d56e504429823daac1d5ea2aeb.json"}}, {"family": "Angelova", "given": "Mihaela", "initials": "M", "orcid": "0000-0002-0495-9695", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d2d1d07f07b24def81b4d5ee64b6c60a.json"}}, {"family": "Puttick", "given": "Clare", "initials": "C"}, {"family": "Zhai", "given": "Haoran", "initials": "H"}, {"family": "Caswell", "given": "Deborah R", "initials": "DR", "orcid": "0000-0002-7550-5092", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/225c5bd5807a44398be2cce8dcc25b52.json"}}, {"family": "Lu", "given": "Wei-Ting", "initials": "WT", "orcid": "0000-0002-1405-4806", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8acbe8b1a0394c668ccf21845b0b673e.json"}}, {"family": "Dietzen", "given": "Michelle", "initials": "M", "orcid": "0000-0002-6853-7563", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4408177a45c844b58fb9ea4f7538d9b9.json"}}, {"family": "Galanos", "given": "Panagiotis", "initials": "P", "orcid": "0000-0003-1403-4685", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9d1071fd28cb42d6b328182cddfd341f.json"}}, {"family": "Evangelou", "given": "Konstantinos", "initials": "K"}, {"family": "Bellelli", "given": "Roberto", "initials": "R"}, {"family": "Lim", "given": "Emilia L", "initials": "EL"}, {"family": "Watkins", "given": "Thomas B K", "initials": "TBK"}, {"family": "Rowan", "given": "Andrew", "initials": "A"}, {"family": "Teixeira", "given": "Vitor H", "initials": "VH"}, {"family": "Zhao", "given": "Yue", "initials": "Y"}, {"family": "Chen", "given": "Haiquan", "initials": "H", "orcid": "0000-0003-1689-0549", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/cdc6fa9477f94f12a85b5034d7728fff.json"}}, {"family": "Ngo", "given": "Bryan", "initials": "B"}, {"family": "Zalmas", "given": "Lykourgos-Panagiotis", "initials": "LP", "orcid": "0000-0002-4317-7709", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e669bc02b2544f9cb61ac71d69f91a81.json"}}, {"family": "Al Bakir", "given": "Maise", "initials": "M"}, {"family": "Hobor", "given": "Sebastijan", "initials": "S"}, {"family": "Gr\u00f6nroos", "given": "Eva", "initials": "E", "orcid": "0000-0001-8303-5409", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1fa0868fdf094f1da9bd53d4ea2b0b5d.json"}}, {"family": "Pennycuick", "given": "Adam", "initials": "A", "orcid": "0000-0001-5836-0250", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f4eb0288b96e4807b1b119c754b7aca1.json"}}, {"family": "Nigro", "given": "Ersilia", "initials": "E"}, {"family": "Campbell", "given": "Brittany B", "initials": "BB"}, {"family": "Brown", "given": "William L", "initials": "WL", "orcid": "0000-0001-5354-9468", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/624b4fe15f824b74879cf42fa268e513.json"}}, {"family": "Akarca", "given": "Ayse U", "initials": "AU", "orcid": "0000-0003-0629-3927", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/bef78ecdb9fc4468bc0ffdbf923662e0.json"}}, {"family": "Marafioti", "given": "Teresa", "initials": "T", "orcid": "0000-0003-1223-6275", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8b9e1588b9284cdeb7e70851280c0d6b.json"}}, {"family": "Wu", "given": "Mary Y", "initials": "MY", "orcid": "0000-0002-2074-6171", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3230e045491e4089b405c8eddba57e12.json"}}, {"family": "Howell", "given": "Michael", "initials": "M", "orcid": "0000-0003-0912-0079", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/111f5b9b742640e5b51e15b8b0873a95.json"}}, {"family": "Boulton", "given": "Simon J", "initials": "SJ", "orcid": "0000-0002-1125-8977", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/54b9e78ef54347b39a8dd5ec4323837d.json"}}, {"family": "Bertoli", "given": "Cosetta", "initials": "C"}, {"family": "Fenton", "given": "Tim R", "initials": "TR", "orcid": "0000-0002-4737-8233", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ea5c50a61a3747b99fd706c00ab6bafe.json"}}, {"family": "de Bruin", "given": "Robertus A M", "initials": "RAM", "orcid": "0000-0001-9957-1409", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/50a1997f1625452b862d9ecaf48f3036.json"}}, {"family": "Maya-Mendoza", "given": "Apolinar", "initials": "A", "orcid": "0000-0001-7452-9896", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8120d9952114478b9909d9906e0dd543.json"}}, {"family": "Santoni-Rugiu", "given": "Eric", "initials": "E", "orcid": "0000-0002-2283-3535", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/36e80a5162c54a45a4b4e26b4508175d.json"}}, {"family": "Hynds", "given": "Robert E", "initials": "RE", "orcid": "0000-0002-2170-8791", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d363c63598224cb0bd24dffc46d0d3eb.json"}}, {"family": "Gorgoulis", "given": "Vassilis G", "initials": "VG", "orcid": "0000-0001-9001-4112", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4f7462e5c510438485b3fa91671db801.json"}}, {"family": "Jamal-Hanjani", "given": "Mariam", "initials": "M"}, {"family": "McGranahan", "given": "Nicholas", "initials": "N"}, {"family": "Harris", "given": "Reuben S", "initials": "RS"}, {"family": "Janes", "given": "Sam M", "initials": "SM", "orcid": "0000-0002-6634-5939", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/310b5ae62b03414d8cc9169b827057c6.json"}}, {"family": "Bartkova", "given": "Jirina", "initials": "J"}, {"family": "Bakhoum", "given": "Samuel F", "initials": "SF"}, {"family": "Bartek", "given": "Jiri", "initials": "J"}, {"family": "Kanu", "given": "Nnennaya", "initials": "N"}, {"family": "Swanton", "given": "Charles", "initials": "C", "orcid": "0000-0002-4299-3018", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e624db9004da4812a607b34b20cea0e7.json"}}, {"family": "TRACERx Consortium", "given": "", "initials": ""}], "type": "journal article", "published": "2021-10-00", "journal": {"title": "Cancer Discov", "issn": "2159-8290", "volume": "11", "issue": "10", "pages": "2456-2473", "issn-l": "2159-8274"}, "abstract": "APOBEC3 enzymes are cytosine deaminases implicated in cancer. Precisely when APOBEC3 expression is induced during cancer development remains to be defined. Here we show that specific APOBEC3 genes are upregulated in breast ductal carcinoma in situ, and in preinvasive lung cancer lesions coincident with cellular proliferation. We observe evidence of APOBEC3-mediated subclonal mutagenesis propagated from TRACERx preinvasive to invasive non-small cell lung cancer (NSCLC) lesions. We find that APOBEC3B exacerbates DNA replication stress and chromosomal instability through incomplete replication of genomic DNA, manifested by accumulation of mitotic ultrafine bridges and 53BP1 nuclear bodies in the G1 phase of the cell cycle. Analysis of TRACERx NSCLC clinical samples and mouse lung cancer models revealed APOBEC3B expression driving replication stress and chromosome missegregation. We propose that APOBEC3 is functionally implicated in the onset of chromosomal instability and somatic mutational heterogeneity in preinvasive disease, providing fuel for selection early in cancer evolution. SIGNIFICANCE: This study reveals the dynamics and drivers of APOBEC3 gene expression in preinvasive disease and the exacerbation of cellular diversity by APOBEC3B through DNA replication stress to promote chromosomal instability early in cancer evolution.This article is highlighted in the In This Issue feature, p. 2355.", "doi": "10.1158/2159-8290.CD-20-0725", "pmid": "33947663", "labels": [], "xrefs": [{"db": "mid", "key": "NIHMS1710791"}, {"db": "pmc", "key": "PMC8487921"}, {"db": "pii", "key": "2159-8290.CD-20-0725"}], "notes": [], "created": "2026-08-20T12:14:28.881Z", "modified": "2026-08-20T12:14:29.593Z"}]}