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Absence of oncogenic canonical pathway mutations in aggressive pediatric rhabdoid tumors
Author(s) -
Kieran Mark W.,
Roberts Charles W.M.,
Chi Susan N.,
Ligon Keith L.,
Rich Benjamin E.,
MacConaill Laura E.,
Garraway Levi A.,
Biegel Jaclyn A.
Publication year - 2012
Publication title -
pediatric blood and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.116
H-Index - 105
eISSN - 1545-5017
pISSN - 1545-5009
DOI - 10.1002/pbc.24315
Subject(s) - smarcb1 , neuroblastoma ras viral oncogene homolog , medicine , cancer research , smarca4 , epigenetics , targeted therapy , mutation , suppressor , atypical teratoid rhabdoid tumor , allele , gene , cancer , pathology , bioinformatics , genetics , biology , chromatin remodeling , medulloblastoma , kras
Background Rhabdoid tumors (also called atypical teratoid/rhabdoid tumor (AT/RT) in the brain), are highly malignant, poor prognosis lesions arising in the kidneys, soft tissues, and central nervous system. Targeted therapy in this disease would benefit from advanced technologies detecting relevant actionable mutations. Procedure Here we report on the evaluation of 25 tumors, all with known SMARCB1/INI1 alterations, for the presence of 983 different mutations in 115 oncogenes and tumor‐suppressor genes using OncoMap, a mass spectrometric method of allele detection. Results Other than mutations in SMARCB1 , our results identified a single activating mutation in NRAS and complete absence of oncogenic mutations in all other genes tested. Conclusion The absence of mutations in canonical pathways critical for development and progression of adult cancers suggests that distinct mechanisms drive these highly malignant pediatric tumors. This may limit the therapeutic utility of available targeted therapies and require a refocusing toward developmental and epigenetic pathways. Pediatr Blood Cancer 2012; 59: 1155–1157. © 2012 Wiley Periodicals, Inc.