[Abnormalities of chromosome 8, APC and beta-catenin genes in aggressive fibromatosis].
OBJECTIVE
To explore the role of abnormalities of chromosome 8, APC and beta-catenin genes in tumorigenesis of aggressive fibromatosis.


METHODS
Trisomy 8 was detected by interphase fluorescence in situ hybridization (FISH). The APC gene and beta-catenin gene mutations were detected by denaturing high performance liquid chromatography (DHPLC) and direct sequence analysis after the PCR transition.


RESULTS
The rate of trisomy 8 in recurrent tumors (62.5%, 5/8) was significantly higher than that in the primary tumors (8.3%, 1/12). Somatic substitution of APC gene was found in 18 of 69 (26.1%) aggressive fibrometases. Somatic transition of beta-catenin gene was detected in 13 of 69 (18.8%) and mutation at codon 41 in exon 3 involving threonine residues implicated in the degradation of beta-catenin. The abnormal expression of beta-catenin had no significant correlation with the mutation of APC or beta-catenin gene. The group with positively expressed beta-catenin protein showed a significant higher c-myc protein expression than those without (P = 0.001). The Ki-67 index was extremely low in all the lesions. The apoptosis index (AI) of the groups with positively expressed c-myc and cyclin D1 showed significantly lower AI than those without.


CONCLUSIONS
Trisomy 8 may serve as a useful predictor of recurrence in aggressive fibromatosis. There are somatic mutations of the APC and beta-catenin genes in the aggressive fibromatosis, and there are abnormalities in the Wnt signaling pathway. These abnormalities may result in the aberrances of cell proliferation and apoptosis, which are likely to be import factors in the tumorigenesis.
Yang
Ji-Long
JL
Department of Pathology, Cancer Hospital, Fudan University, Shanghai 200032, China.
Wang
Jian
J
Zhou
Xiao-Yan
XY
Zhu
Xiong-Zeng
XZ
D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics* / Q000378:metabolism; D017209:Apoptosis; D002898:Chromosomes, Human, Pair 8; D019938:Cyclin D1 / Q000378:metabolism; D018222:Desmoid Tumors / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D017491:Genes, APC; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D009364:Neoplasm Recurrence, Local; D017354:Point Mutation; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D015398:Signal Transduction; D014314:Trisomy; D051153:Wnt Proteins / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics* / Q000378:metabolism
D025601:Adenomatous Polyposis Coli Protein; D019394:Ki-67 Antigen; D016271:Proto-Oncogene Proteins c-myc; D051153:Wnt Proteins; D051176:beta Catenin; D019938:Cyclin D1