دورية أكاديمية
Single-cell genomic variation induced by mutational processes in cancer.
| العنوان: | Single-cell genomic variation induced by mutational processes in cancer. |
|---|---|
| المؤلفون: | Funnell T; Tri-Institutional PhD Program in Computational Biology and Medicine, Weill Cornell Medicine, New York, NY, USA.; Computational Oncology, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA., O'Flanagan CH; Department of Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia, Canada., Williams MJ; Computational Oncology, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA. william1@mskcc.org., McPherson A; Computational Oncology, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA., McKinney S; Department of Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia, Canada., Kabeer F; Department of Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia, Canada.; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada., Lee H; Department of Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia, Canada.; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada., Salehi S; Computational Oncology, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Vázquez-García I; Computational Oncology, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Shi H; Computational Oncology, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Leventhal E; Computational Oncology, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Masud T; Department of Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia, Canada., Eirew P; Department of Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia, Canada., Yap D; Department of Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia, Canada., Zhang AW; Department of Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia, Canada., Lim JLP; Computational Oncology, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Wang B; Department of Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia, Canada., Brimhall J; Department of Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia, Canada., Biele J; Department of Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia, Canada., Ting J; Department of Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia, Canada., Au V; Department of Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia, Canada., Van Vliet M; Department of Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia, Canada., Liu YF; Department of Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia, Canada., Beatty S; Department of Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia, Canada., Lai D; Department of Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia, Canada.; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada., Pham J; Department of Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia, Canada., Grewal D; Computational Oncology, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Abrams D; Computational Oncology, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Havasov E; Computational Oncology, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Leung S; Computational Oncology, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Bojilova V; Computational Oncology, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Moore RA; Michael Smith Genome Sciences Centre, Vancouver, British Columbia, Canada., Rusk N; Computational Oncology, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Uhlitz F; Computational Oncology, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Ceglia N; Computational Oncology, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Weiner AC; Tri-Institutional PhD Program in Computational Biology and Medicine, Weill Cornell Medicine, New York, NY, USA.; Computational Oncology, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Zaikova E; Department of Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia, Canada., Douglas JM; Department of Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia, Canada., Zamarin D; GYN Medical Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Weigelt B; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Kim SH; Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Da Cruz Paula A; Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Reis-Filho JS; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Martin SD; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada., Li Y; Department of Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia, Canada., Xu H; Department of Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia, Canada., de Algara TR; Department of Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia, Canada., Lee SR; Department of Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia, Canada., Llanos VC; Department of Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia, Canada., Huntsman DG; Department of Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia, Canada.; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada., McAlpine JN; Department of Gynecology and Obstetrics, University of British Columbia, Vancouver, British Columbia, Canada., Shah SP; Computational Oncology, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA. shahs3@mskcc.org., Aparicio S; Department of Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia, Canada. saparicio@bccrc.ca.; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada. saparicio@bccrc.ca. |
| مؤلفون مشاركون: | IMAXT Consortium |
| المصدر: | Nature [Nature] 2022 Dec; Vol. 612 (7938), pp. 106-115. Date of Electronic Publication: 2022 Oct 26. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Nature Publishing Group Country of Publication: England NLM ID: 0410462 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-4687 (Electronic) Linking ISSN: 00280836 NLM ISO Abbreviation: Nature Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Basingstoke : Nature Publishing Group Original Publication: London, Macmillan Journals ltd. |
| مواضيع طبية MeSH: | Genomics* , Mutation* , Ovarian Neoplasms*/genetics , Ovarian Neoplasms*/pathology , Triple Negative Breast Neoplasms*/genetics , Triple Negative Breast Neoplasms*/pathology , Single-Cell Analysis*, Female ; Humans ; Phylogeny |
| مستخلص: | How cell-to-cell copy number alterations that underpin genomic instability 1 in human cancers drive genomic and phenotypic variation, and consequently the evolution of cancer 2 , remains understudied. Here, by applying scaled single-cell whole-genome sequencing 3 to wild-type, TP53-deficient and TP53-deficient;BRCA1-deficient or TP53-deficient;BRCA2-deficient mammary epithelial cells (13,818 genomes), and to primary triple-negative breast cancer (TNBC) and high-grade serous ovarian cancer (HGSC) cells (22,057 genomes), we identify three distinct 'foreground' mutational patterns that are defined by cell-to-cell structural variation. Cell- and clone-specific high-level amplifications, parallel haplotype-specific copy number alterations and copy number segment length variation (serrate structural variations) had measurable phenotypic and evolutionary consequences. In TNBC and HGSC, clone-specific high-level amplifications in known oncogenes were highly prevalent in tumours bearing fold-back inversions, relative to tumours with homologous recombination deficiency, and were associated with increased clone-to-clone phenotypic variation. Parallel haplotype-specific alterations were also commonly observed, leading to phylogenetic evolutionary diversity and clone-specific mono-allelic expression. Serrate variants were increased in tumours with fold-back inversions and were highly correlated with increased genomic diversity of cellular populations. Together, our findings show that cell-to-cell structural variation contributes to the origins of phenotypic and evolutionary diversity in TNBC and HGSC, and provide insight into the genomic and mutational states of individual cancer cells. (© 2022. The Author(s).) |
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| معلومات مُعتمدة: | K99 CA256508 United States CA NCI NIH HHS; P30 CA008748 United States CA NCI NIH HHS; RM1 HG011014 United States HG NHGRI NIH HHS; United Kingdom CRUK_ Cancer Research UK |
| فهرسة مساهمة: | Investigator: GJ Hannon; G Battistoni; D Bressan; IG Cannell; H Casbolt; C Jauset; T Kovačević; CM Mulvey; F Nugent; MP Ribes; I Pearson; F Qosaj; K Sawicka; SA Wild; E Williams; E Laks; A Smith; D Lai; A Roth; S Balasubramanian; M Lee; B Bodenmiller; M Burger; L Kuett; S Tietscher; J Windhager; ES Boyden; S Alon; Y Cui; A Emenari; DR Goodwin; ED Karagiannis; A Sinha; AT Wassie; C Caldas; A Bruna; M Callari; W Greenwood; G Lerda; Y Eyal-Lubling; OM Rueda; A Shea; O Harris; R Becker; F Grimaldo; S Harris; SL Vogl; JA Joyce; SS Watson; S Tavare; KN Dinh; E Fisher; R Kunes; NA Walton; M Al Sa'd; N Chornay; A Dariush; EA González-Solares; C González-Fernández; AK Yoldaş; N Miller; X Zhuang; J Fan; H Lee; LA Sepúlveda; C Xia; P Zheng |
| المشرفين على المادة: | 0 (TP53 protein, human) 0 (BRCA1 protein, human) 0 (BRCA2 protein, human) |
| تواريخ الأحداث: | Date Created: 20221026 Date Completed: 20221214 Latest Revision: 20240524 |
| رمز التحديث: | 20240524 |
| مُعرف محوري في PubMed: | PMC9712114 |
| DOI: | 10.1038/s41586-022-05249-0 |
| PMID: | 36289342 |
| قاعدة البيانات: | MEDLINE |
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| DOI: | 10.1038/s41586-022-05249-0 |