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Molecular characterization by array comparative genomic hybridization and DNA sequencing of 194 desmoid tumors
Author(s) -
Salas Sébastien,
Chibon Frederic,
Noguchi Tetsuro,
Terrier Philippe,
RanchereVince Dominique,
Lagarde Pauline,
Benard Jean,
Forget Sébastien,
Blanchard Camille,
Dômont Julien,
Bonvalot Sylvie,
Guillou Louis,
Leroux Agnès,
MechineNeuville Agnes,
Schöffski Patrick,
Laë Marik,
Collin Françoise,
Verola Olivier,
Carbonnelle Amelie,
Vescovo Laure,
Bui Binh,
Brouste Véronique,
Sobol Hagay,
Aurias Alain,
Coindre JeanMichel
Publication year - 2010
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.20766
Subject(s) - comparative genomic hybridization , biology , fluorescence in situ hybridization , carcinogenesis , locus (genetics) , cancer research , karyotype , fibromatosis , pathology , chromosome , genetics , gene , medicine
Desmoid tumors are fibroblastic/myofibroblastic proliferations. Previous studies reported that CTNNB1 mutations were detected in 84% and that mutations of the APC gene were found in several cases of sporadic desmoid tumors lacking CTNNB1 mutations. Forty tumors were analyzed by comparative genomic hybridization (CGH). Karyotype and fluorescence in situ hybridization revealed a nonrandom occurrence of trisomy 8 associated with an increased risk of recurrence. We report the first molecular characterization including a large series of patients. We performed array CGH on frozen samples of 194 tumors, and we screened for APC mutations in patients without CNNTB1 mutation. A high frequency of genomically normal tumors was observed. Four relevant and recurrent alterations (loss of 6q, loss of 5q, gain of 20q, and gain of Chromosome 8) were found in 40 out of 46 tumors with chromosomal changes. Gain of Chromosomes 8 and 20 was not associated with an increased risk of recurrence. Cases with loss of 5q had a minimal common region in 5q22.5 including the APC locus. Alterations of APC , including loss of the entire locus, and CTNNB1 mutation could explain the tumorigenesis in 89% of sporadic desmoids tumors and desmoids tumors occurring in the context of Gardner's syndrome. A better understanding of the pathogenetic pathways in the initiation and progression of desmoid tumors requires studies of 8q and 20q gains, as well as of 6q and 5q losses, and study of the Wnt/β‐catenin pathway. © 2010 Wiley‐Liss, Inc.