| Literature DB >> 34308366 |
Elise M Fiala1,2, Gowtham Jayakumaran3, Audrey Mauguen4, Jennifer A Kennedy1,2, Nancy Bouvier1, Yelena Kemel5, Megan Harlan Fleischut2, Anna Maio2, Erin E Salo-Mullen2, Margaret Sheehan2, Angela G Arnold2, Alicia Latham2, Maria I Carlo2, Karen Cadoo2, Semanti Murkherjee2, Emily K Slotkin1, Tanya Trippett1, Julia Glade Bender1, Paul A Meyers1, Leonard Wexler1, Filemon S Dela Cruz1, Nai-Kong Cheung1, Ellen Basu1, Alex Kentsis1, Michael Ortiz1, Jasmine H Francis6, Ira J Dunkel1, Yasmin Khakoo1, Stephen Gilheeney1, Sameer Farouk Sait1, Christopher J Forlenza1, Maria Sulis1, Matthias Karajannis1, Shakeel Modak1, Justin T Gerstle6, Todd E Heaton6, Stephen Roberts1, Ciyu Yang3, Sowmya Jairam3, Joseph Vijai2, Sabine Topka5, Danielle N Friedman1, Zsofia K Stadler2, Mark Robson2, Michael F Berger3, Nikolaus Schultz4, Marc Ladanyi3, Richard J O'Reilly1, David H Abramson6, Ozge Ceyhan-Birsoy3, Liying Zhang3, Diana Mandelker3, Neerav N Shukla1, Andrew L Kung1, Kenneth Offit2, Ahmet Zehir7, Michael F Walsh8,9.
Abstract
The spectrum of germline predisposition in pediatric cancer continues to be realized. Here we report 751 solid tumor patients who underwent prospective matched tumor-normal DNA sequencing and downstream clinical use (clinicaltrials.gov 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 13% (99/751) in moderate and high penetrance dominant genes. 34% of high or moderate penetrance variants were unexpected based on the patient's diagnosis and previous history. 76% 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 use of targeted therapies. Germline testing should be considered for all children with cancer.Entities:
Mesh：
Year: 2021 PMID： 34308366 PMCID： PMC8294573 DOI： 10.1038/s43018-021-00172-1
Source DB: PubMed Journal: Nat Cancer ISSN： 2662-1347