Comprehensive Analysis of Genetic Ancestry and Its Molecular Correlates in Cancer.,Cancer Cell

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Comprehensive Analysis of Genetic Ancestry and Its Molecular Correlates in Cancer.
Cancer Cell ( IF 50.3 ) Pub Date : 2020-05-11 , DOI: 10.1016/j.ccell.2020.04.012
Jian Carrot-Zhang ₁ , Nyasha Chambwe ₂ , Jeffrey S Damrauer ₃ , Theo A Knijnenburg ₂ , A Gordon Robertson ₄ , Christina Yau ₅ , Wanding Zhou ₆ , Ashton C Berger ₇ , Kuan-Lin Huang ₈ , Justin Y Newberg ₉ , R Jay Mashl ₁₀ , Alessandro Romanel ₁₁ , Rosalyn W Sayaman ₁₂ , Francesca Demichelis ₁₁ , Ina Felau ₁₃ , Garrett M Frampton ₉ , Seunghun Han ₁₄ , Katherine A Hoadley ₃ , Anab Kemal ₁₃ , Peter W Laird ₆ , Alexander J Lazar ₁₅ , Xiuning Le ₁₆ , Ninad Oak ₁₇ , Hui Shen ₆ , Christopher K Wong ₁₈ , Jean C Zenklusen ₁₃ , Elad Ziv ₁₉ , , Andrew D Cherniack ₁ , Rameen Beroukhim ₂₀

Affiliation

The Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Harvard Medical School, Boston, MA 02115, USA.
Institute for Systems Biology, Seattle, WA 98109, USA.
Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
British Columbia Cancer Agency, Genome Sciences Centre, Vancouver, BC V5Z4S6, Canada.
Buck Institute for Research on Aging, Novato, CA 94945, USA; Department of Surgery, University of California, San Francisco, San Francisco, CA 94115, USA.
Van Andel Research Institute, Grand Rapids, MI 49503, USA.
The Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Department of Genetics and Genomics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Foundation Medicine, Cambridge, MA 02141, USA.
Department of Medicine, Washington University in St. Louis, St. Louis, MO 63110, USA.
Department of Cellular, Computational and Integrative Biology (CIBIO), University of Trento, Via Sommarive 9, 38123 Povo (Trento), Italy.
Department of Laboratory Medicine, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Population Sciences, Beckman Research Institute, City of Hope, Duarte, CA 91010, USA.
National Cancer Institute, Bethesda, MD 20892, USA.
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Harvard Medical School, Boston, MA 02115, USA.
Departments of Pathology, Genomic Medicine, and Translational Molecular Pathology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Department of Thoracic and Head and Neck Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
UC Santa Cruz Genomics Institute, University of California, Santa Cruz, Santa Cruz, CA 95064, USA.
Department of Laboratory Medicine, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94143, USA.
The Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Harvard Medical School, Boston, MA 02115, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.

We evaluated ancestry effects on mutation rates, DNA methylation, and mRNA and miRNA expression among 10,678 patients across 33 cancer types from The Cancer Genome Atlas. We demonstrated that cancer subtypes and ancestry-related technical artifacts are important confounders that have been insufficiently accounted for. Once accounted for, ancestry-associated differences spanned all molecular features and hundreds of genes. Biologically significant differences were usually tissue specific but not specific to cancer. However, admixture and pathway analyses suggested some of these differences are causally related to cancer. Specific findings included increased FBXW7 mutations in patients of African origin, decreased VHL and PBRM1 mutations in renal cancer patients of African origin, and decreased immune activity in bladder cancer patients of East Asian origin.

中文翻译：

遗传祖先及其在癌症中的分子相关性的综合分析。

我们评估了祖先对癌症基因组图谱中 33 种癌症类型的 10,678 名患者的突变率、DNA 甲基化以及 mRNA 和 miRNA 表达的影响。我们证明了癌症亚型和与血统相关的技术人工制品是重要的混杂因素，但尚未得到充分解释。一旦考虑在内，与血统相关的差异就涵盖了所有分子特征和数百个基因。生物学上的显着差异通常是组织特异性的，而不是癌症特异性的。然而，混合物和通路分析表明，其中一些差异与癌症有因果关系。具体发现包括非洲裔患者的 FBXW7 突变增加，非洲裔肾癌患者的 VHL 和 PBRM1 突变减少，

更新日期：2020-05-11

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