Near universal detection of alterations in CTNNB1 and Wnt pathway regulators in desmoid‐type fibromatosis by whole‐exome sequencing and genomic analysis

• DOI: 10.1002/gcc.22272
• Publication Date: 2015-07-14T12:54:14Z
• Authors: Aimee M. Crago; Juliann Chmielecki; Mara Rosenberg; Rachael O'Connor; Caitlin Byrne; Fatima G. Wilder; Katherine Thorn; Phaedra Agius; Deborah Kuk; Nicholas D. Socci; Li‐Xuan Qin; Matthew Meyerson; Meera Hameed; Samuel Singer
• Keywords: Sanger sequencing; Wild type

CTNNB1 mutations or APC abnormalities have been observed in ∼85% of desmoids examined by Sanger sequencing and are associated with Wnt/β‐catenin activation. We sought to identify molecular aberrations “wild‐type” tumors (those without alteration) determine their prognostic relevance. was 117 desmoids; a mutation 101 (86%) 16 were wild type. Wild‐type status did not associate tumor recurrence. Moreover, unsupervised clustering based on U133A‐derived gene expression profiles, wild‐type mutated clustered together. Whole‐exome eight the revealed that three had undetected sequencing. The found mean 16% reads (vs. 37% for identified Sanger). Of other five sequenced, two loss, chromosome 6 one BMI1 . finding low‐frequency loss validated remaining directed miSeq four comparative genomic hybridization one. These results demonstrate affecting occur more frequently than previously recognized (111 117; 95%), designation genotype is largely determined sensitivity detection methods. Even true (determined next‐generation sequencing) may alterations Wnt activation (chromosome loss/ mutation), supporting as common pathway governing desmoid initiation. © 2015 Wiley Periodicals, Inc.