Prospective pan-cancer germline testing using MSK-IMPACT informs clinical translation in 751 patients with pediatric solid tumors

Elise M. Fiala, Gowtham Jayakumaran, Audrey Mauguen, Jennifer A. Kennedy, Nancy Bouvier, Yelena Kemel, Megan Harlan Fleischut, Anna Maio, Erin E. Salo-Mullen, Margaret Sheehan, Angela G. Arnold, Alicia Latham, Maria I. Carlo, Karen Cadoo, Semanti Murkherjee, Emily K. Slotkin, Tanya Trippett, Julia Glade Bender, Paul A. Meyers, Leonard WexlerFilemon S. Dela Cruz, Nai Kong Cheung, Ellen Basu, Alex Kentsis, Michael Ortiz, Jasmine H. Francis, Ira J. Dunkel, Yasmin Khakoo, Stephen Gilheeney, Sameer Farouk Sait, Christopher J. Forlenza, Maria Sulis, Matthias Karajannis, Shakeel Modak, Justin T. Gerstle, Todd E. Heaton, Stephen Roberts, Ciyu Yang, Sowmya Jairam, Joseph Vijai, Sabine Topka, Danielle N. Friedman, Zsofia K. Stadler, Mark Robson, Michael F. Berger, Nikolaus Schultz, Marc Ladanyi, Richard J. O’Reilly, David H. Abramson, Ozge Ceyhan-Birsoy

Research output: Contribution to journalArticlepeer-review


The spectrum of germline predisposition in pediatric cancer continues to be realized. Here we report 751 patients with solid tumors who underwent prospective matched tumor–normal DNA sequencing with downstream clinical use ( NCT01775072). Germline pathogenic and likely pathogenic (P/LP) variants were reported. One or more P/LP variants were found in 18% (138/751) of individuals when including variants in low-, moderate- and high-penetrance dominant or recessive genes or in 13% (99/751) of individuals in moderate- and high-penetrance dominant genes. Thirty-four percent of high- or moderate-penetrance variants were unexpected based on the patient’s diagnosis and previous history. Seventy-six percent of patients with positive results completed a clinical genetics visit, and 21% had at least one relative undergo cascade testing as a result of this testing. Clinical actionability additionally included screening, risk reduction in relatives, reproductive use and targeted therapies. Germline testing should be considered for all children with cancer.

Original languageEnglish
JournalNature Cancer
Publication statusAccepted/In press - 2021

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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