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

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

Authors:	Fiala, E. M.; Jayakumaran, G.; Mauguen, A.; Kennedy, J. A.; Bouvier, N.; Kemel, Y.; Fleischut, M. H.; Maio, A.; Salo-Mullen, E. E.; Sheehan, M.; Arnold, A. G.; Latham, A.; Carlo, M. I.; Cadoo, K.; Murkherjee, S.; Slotkin, E. K.; Trippett, T.; Glade Bender, J.; Meyers, P. A.; Wexler, L.; Dela Cruz, F. S.; Cheung, N. K.; Basu, E.; Kentsis, A.; Ortiz, M.; Francis, J. H.; Dunkel, I. J.; Khakoo, Y.; Gilheeney, S.; Farouk Sait, S.; Forlenza, C. J.; Sulis, M.; Karajannis, M.; Modak, S.; Gerstle, J. T.; Heaton, T. E.; Roberts, S.; Yang, C.; Jairam, S.; Vijai, J.; Topka, S.; Friedman, D. N.; Stadler, Z. K.; Robson, M.; Berger, M. F.; Schultz, N.; Ladanyi, M.; O’Reilly, R. J.; Abramson, D. H.; Ceyhan-Birsoy, O.; Zhang, L.; Mandelker, D.; Shukla, N. N.; Kung, A. L.; Offit, K.; Zehir, A.; Walsh, M. F.
Article Title:	Prospective pan-cancer germline testing using MSK-IMPACT informs clinical translation in 751 patients with pediatric solid tumors
Abstract:	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 (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 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. © 2021, The Author(s), under exclusive licence to Springer Nature America, Inc. part of Springer Nature.
Journal Title:	Nature Cancer
Volume:	2
Issue:	3
ISSN:	2662-1347
Publisher:	Nature Research
Date Published:	2021-03-01
Start Page:	357
End Page:	365
Language:	English
DOI:	10.1038/s43018-021-00172-1
PROVIDER:	scopus
PMCID:	PMC8294573
PUBMED:	34308366
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85101429889&doi=10.1038%2fs43018-021-00172-1&partnerID=40&md5=c602355696b705103606cfc6790bd9bf
Notes:	Semanti Mukherjee's name is misspelled on the original publication; Vijai Joseph's first and last names are reversed on the original publication -- Article -- Export Date: 3 May 2021 -- Source: Scopus