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Clinical cancer genomic profiling by three-platform sequencing of whole genome, whole exome and transcriptome

Author

Listed:
  • Michael Rusch

    (St. Jude Children’s Research Hospital
    St. Jude Children’s Research Hospital)

  • Joy Nakitandwe

    (St. Jude Children’s Research Hospital
    St. Jude Children’s Research Hospital)

  • Sheila Shurtleff

    (St. Jude Children’s Research Hospital
    St. Jude Children’s Research Hospital)

  • Scott Newman

    (St. Jude Children’s Research Hospital
    St. Jude Children’s Research Hospital)

  • Zhaojie Zhang

    (St. Jude Children’s Research Hospital
    St. Jude Children’s Research Hospital)

  • Michael N. Edmonson

    (St. Jude Children’s Research Hospital
    St. Jude Children’s Research Hospital)

  • Matthew Parker

    (University of Sheffield)

  • Yuannian Jiao

    (St. Jude Children’s Research Hospital
    St. Jude Children’s Research Hospital)

  • Xiaotu Ma

    (St. Jude Children’s Research Hospital
    St. Jude Children’s Research Hospital)

  • Yanling Liu

    (St. Jude Children’s Research Hospital
    St. Jude Children’s Research Hospital)

  • Jiali Gu

    (St. Jude Children’s Research Hospital
    St. Jude Children’s Research Hospital)

  • Michael F. Walsh

    (St. Jude Children’s Research Hospital
    St. Jude Children’s Research Hospital)

  • Jared Becksfort

    (St. Jude Children’s Research Hospital
    St. Jude Children’s Research Hospital)

  • Andrew Thrasher

    (St. Jude Children’s Research Hospital
    St. Jude Children’s Research Hospital)

  • Yongjin Li

    (St. Jude Children’s Research Hospital
    St. Jude Children’s Research Hospital)

  • James McMurry

    (St. Jude Children’s Research Hospital
    St. Jude Children’s Research Hospital)

  • Erin Hedlund

    (St. Jude Children’s Research Hospital
    St. Jude Children’s Research Hospital)

  • Aman Patel

    (St. Jude Children’s Research Hospital
    St. Jude Children’s Research Hospital)

  • John Easton

    (St. Jude Children’s Research Hospital
    St. Jude Children’s Research Hospital)

  • Donald Yergeau

    (St. Jude Children’s Research Hospital
    St. Jude Children’s Research Hospital)

  • Bhavin Vadodaria

    (St. Jude Children’s Research Hospital
    St. Jude Children’s Research Hospital)

  • Ruth G. Tatevossian

    (St. Jude Children’s Research Hospital
    St. Jude Children’s Research Hospital)

  • Susana Raimondi

    (St. Jude Children’s Research Hospital
    St. Jude Children’s Research Hospital)

  • Dale Hedges

    (St. Jude Children’s Research Hospital
    St. Jude Children’s Research Hospital)

  • Xiang Chen

    (St. Jude Children’s Research Hospital
    St. Jude Children’s Research Hospital)

  • Kohei Hagiwara

    (St. Jude Children’s Research Hospital
    St. Jude Children’s Research Hospital)

  • Rose McGee

    (St. Jude Children’s Research Hospital
    St. Jude Children’s Research Hospital)

  • Giles W. Robinson

    (St. Jude Children’s Research Hospital
    St. Jude Children’s Research Hospital)

  • Jeffery M. Klco

    (St. Jude Children’s Research Hospital
    St. Jude Children’s Research Hospital)

  • Tanja A. Gruber

    (St. Jude Children’s Research Hospital
    St. Jude Children’s Research Hospital
    St. Jude Children’s Research Hospital)

  • David W. Ellison

    (St. Jude Children’s Research Hospital
    St. Jude Children’s Research Hospital)

  • James R Downing

    (St. Jude Children’s Research Hospital
    St. Jude Children’s Research Hospital)

  • Jinghui Zhang

    (St. Jude Children’s Research Hospital
    St. Jude Children’s Research Hospital)

Abstract

To evaluate the potential of an integrated clinical test to detect diverse classes of somatic and germline mutations relevant to pediatric oncology, we performed three-platform whole-genome (WGS), whole exome (WES) and transcriptome (RNA-Seq) sequencing of tumors and normal tissue from 78 pediatric cancer patients in a CLIA-certified, CAP-accredited laboratory. Our analysis pipeline achieves high accuracy by cross-validating variants between sequencing types, thereby removing the need for confirmatory testing, and facilitates comprehensive reporting in a clinically-relevant timeframe. Three-platform sequencing has a positive predictive value of 97–99, 99, and 91% for somatic SNVs, indels and structural variations, respectively, based on independent experimental verification of 15,225 variants. We report 240 pathogenic variants across all cases, including 84 of 86 known from previous diagnostic testing (98% sensitivity). Combined WES and RNA-Seq, the current standard for precision oncology, achieved only 78% sensitivity. These results emphasize the critical need for incorporating WGS in pediatric oncology testing.

Suggested Citation

  • Michael Rusch & Joy Nakitandwe & Sheila Shurtleff & Scott Newman & Zhaojie Zhang & Michael N. Edmonson & Matthew Parker & Yuannian Jiao & Xiaotu Ma & Yanling Liu & Jiali Gu & Michael F. Walsh & Jared , 2018. "Clinical cancer genomic profiling by three-platform sequencing of whole genome, whole exome and transcriptome," Nature Communications, Nature, vol. 9(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06485-7
    DOI: 10.1038/s41467-018-06485-7
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