title: Familial adenomatous polyposis-associated desmoids display significantly more genetic changes than sporadic desmoids.
abstract: Desmoid tumours (also called deep or aggressive fibromatoses) are potentially life-threatening fibromatous lesions. Hereditary desmoid tumours arise in individuals affected by either familial adenomatous polyposis (FAP) or hereditary desmoid disease (HDD) carrying germline mutations in APC. Most sporadic desmoids carry somatic mutations in CTNNB1. Previous studies identified losses on 5q and 6q, and gains on 8q and 20q as recurrent genetic changes in desmoids. However, virtually all genetic changes were derived from sporadic tumours. To investigate the somatic alterations in FAP-associated desmoids and to compare them with changes occurring in sporadic tumours, we analysed 17 FAP-associated and 38 sporadic desmoids by array comparative genomic hybridisation and multiple ligation-dependent probe amplification. Overall, the desmoids displayed only a limited number of genetic changes, occurring in 44% of cases. Recurrent gains at 8q (7%) and 20q (5%) were almost exclusively found in sporadic tumours. Recurrent losses were observed for a 700 kb region at 5q22.2, comprising the APC gene (11%), a 2 Mb region at 6p21.2-p21.1 (15%), and a relatively large region at 6q15-q23.3 (20%). The FAP-associated desmoids displayed a significantly higher frequency of copy number abnormalities (59%) than the sporadic tumours (37%). As predicted by the APC germline mutations among these patients, a high percentage (29%) of FAP-associated desmoids showed loss of the APC region at 5q22.2, which was infrequently (3%) seen among sporadic tumours. Our data suggest that loss of region 6q15-q16.2 is an important event in FAP-associated as well as sporadic desmoids, most likely of relevance for desmoid tumour progression.
authors.affiliation: Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands. e.c.robanus@lumc.nl
authors.forename: Els
authors.initials: E
authors.lastname: Robanus-Maandag
authors.forename: Cathy
authors.initials: C
authors.lastname: Bosch
authors.forename: Saeid
authors.initials: S
authors.lastname: Amini-Nik
authors.forename: Jeroen
authors.initials: J
authors.lastname: Knijnenburg
authors.forename: Karoly
authors.initials: K
authors.lastname: Szuhai
authors.forename: Pascale
authors.initials: P
authors.lastname: Cervera
authors.forename: Raymond
authors.initials: R
authors.lastname: Poon
authors.forename: Diana
authors.initials: D
authors.lastname: Eccles
authors.forename: Paolo
authors.initials: P
authors.lastname: Radice
authors.forename: Marco
authors.initials: M
authors.lastname: Giovannini
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Alman
authors.forename: Sabine
authors.initials: S
authors.lastname: Tejpar
authors.forename: Peter
authors.initials: P
authors.lastname: Devilee
authors.forename: Riccardo
authors.initials: R
authors.lastname: Fodde
mesh_terms: D000008:Abdominal Neoplasms / Q000150:complications* / Q000235:genetics*; D011125:Adenomatous Polyposis Coli / Q000150:complications* / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics; D055028:Comparative Genomic Hybridization; D005260:Female; D018222:Desmoid Tumors / Q000150:complications* / Q000235:genetics*; D018628:Gene Dosage / Q000235:genetics; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D055815:Young Adult