iScience (Jan 2022)
Peptide ancestry informative markers in uterine neoplasms from women of European, African, and Asian ancestry
- Nicholas W. Bateman,
- Christopher M. Tarney,
- Tamara S. Abulez,
- Brian L. Hood,
- Kelly A. Conrads,
- Ming Zhou,
- Anthony R. Soltis,
- Pang-Ning Teng,
- Amanda Jackson,
- Chunqiao Tian,
- Clifton L. Dalgard,
- Matthew D. Wilkerson,
- Michael D. Kessler,
- Zachary Goecker,
- Jeremy Loffredo,
- Craig D. Shriver,
- Hai Hu,
- Michele Cote,
- Glendon J. Parker,
- James Segars,
- Ayman Al-Hendy,
- John I. Risinger,
- Neil T. Phippen,
- Yovanni Casablanca,
- Kathleen M. Darcy,
- G. Larry Maxwell,
- Thomas P. Conrads,
- Timothy D. O'Connor
Affiliations
- Nicholas W. Bateman
- Gynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA; The John P. Murtha Cancer Center, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., 6720A Rockledge Dr., Suite 100, Bethesda, MD 20817, USA; Corresponding author: 3289 Woodburn Rd, Suite 375, Annandale, VA 22003;
- Christopher M. Tarney
- Gynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA
- Tamara S. Abulez
- Gynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., 6720A Rockledge Dr., Suite 100, Bethesda, MD 20817, USA
- Brian L. Hood
- Gynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., 6720A Rockledge Dr., Suite 100, Bethesda, MD 20817, USA
- Kelly A. Conrads
- Gynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., 6720A Rockledge Dr., Suite 100, Bethesda, MD 20817, USA
- Ming Zhou
- Department of Obstetrics and Gynecology, Inova Fairfax Medical Campus, 3300 Gallows Road, Falls Church, VA 22042, USA
- Anthony R. Soltis
- Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., 6720A Rockledge Dr., Suite 100, Bethesda, MD 20817, USA; The American Genome Center; Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA
- Pang-Ning Teng
- Gynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., 6720A Rockledge Dr., Suite 100, Bethesda, MD 20817, USA
- Amanda Jackson
- Gynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA
- Chunqiao Tian
- Gynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., 6720A Rockledge Dr., Suite 100, Bethesda, MD 20817, USA
- Clifton L. Dalgard
- The American Genome Center; Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA; Department of Anatomy Physiology and Genetics, Uniformed Services University, 4301 Jones Bridge Road, Bethesda, MD 20814, USA
- Matthew D. Wilkerson
- The John P. Murtha Cancer Center, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., 6720A Rockledge Dr., Suite 100, Bethesda, MD 20817, USA; The American Genome Center; Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA; Department of Anatomy Physiology and Genetics, Uniformed Services University, 4301 Jones Bridge Road, Bethesda, MD 20814, USA
- Michael D. Kessler
- Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD 21201, USA
- Zachary Goecker
- University of California, Davis, One Shields Avenue, Davis, CA 95616, USA
- Jeremy Loffredo
- Gynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA
- Craig D. Shriver
- The John P. Murtha Cancer Center, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA
- Hai Hu
- The John P. Murtha Cancer Center, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA; Chan Soon-Shiong Institute of Molecular Medicine at Windber, Windber, PA 15963, USA
- Michele Cote
- Wayne State University, Detroit, MI 48202, USA
- Glendon J. Parker
- University of California, Davis, One Shields Avenue, Davis, CA 95616, USA
- James Segars
- Johns Hopkins University Medical Center, Baltimore, MD 21218, USA
- Ayman Al-Hendy
- The University of Illinois College of Medicine, Chicago, IL 60612, USA
- John I. Risinger
- Department of Obstetrics and Gynecology, Michigan State University, East Lansing, MI 48824, USA
- Neil T. Phippen
- Gynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA; The John P. Murtha Cancer Center, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA
- Yovanni Casablanca
- Gynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA; The John P. Murtha Cancer Center, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA
- Kathleen M. Darcy
- Gynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA; The John P. Murtha Cancer Center, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., 6720A Rockledge Dr., Suite 100, Bethesda, MD 20817, USA
- G. Larry Maxwell
- Gynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA; The John P. Murtha Cancer Center, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA; Department of Obstetrics and Gynecology, Inova Fairfax Medical Campus, 3300 Gallows Road, Falls Church, VA 22042, USA
- Thomas P. Conrads
- Gynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA; The John P. Murtha Cancer Center, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA; Department of Obstetrics and Gynecology, Inova Fairfax Medical Campus, 3300 Gallows Road, Falls Church, VA 22042, USA
- Timothy D. O'Connor
- Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD 21201, USA; Program in Personalize and Genomic Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA; Marlene and Stewart Greenebaum Comprehensive Cancer, University of Maryland School of Medicine, Baltimore, MD 21201, USA
- Journal volume & issue
-
Vol. 25,
no. 1
p. 103665
Abstract
Summary: Characterization of ancestry-linked peptide variants in disease-relevant patient tissues represents a foundational step to connect patient ancestry with disease pathogenesis. Nonsynonymous single-nucleotide polymorphisms encoding missense substitutions within tryptic peptides exhibiting high allele frequencies in European, African, and East Asian populations, termed peptide ancestry informative markers (pAIMs), were prioritized from 1000 genomes. In silico analysis identified that as few as 20 pAIMs can determine ancestry proportions similarly to >260K SNPs (R2 = 0.99). Multiplexed proteomic analysis of >100 human endometrial cancer cell lines and uterine leiomyoma tissues combined resulted in the quantitation of 62 pAIMs that correlate with patient race and genotype-confirmed ancestry. Candidates include a D451E substitution in GC vitamin D-binding protein previously associated with altered vitamin D levels in African and European populations. pAIMs will support generalized proteoancestry assessment as well as efforts investigating the impact of ancestry on the human proteome and how this relates to the pathogenesis of uterine neoplasms.
