title: Brain metastases exhibit gross deletions of the APC gene.
abstract: Candidate genes involved in metastasis to the brain require investigation. In the present study, the adenomatous polyposis coli (APC) gene was analyzed in a set of human brain metastases. Gross deletions of the APC gene were tested by polymerase chain reaction/loss of heterozygosity (LOH) using the restriction fragment length polymorphism method performed by the use of MspI and RsaI genetic markers inside exon 15 and exon 11. Among 21 brain metastases analyzed, 58.8% of samples showed LOH of the APC gene. When assigning the genetic changes to a specific primary tumor type, 6 LOHs were found in metastases originated from lung and 4 LOHs in metastases from colon. The main effector of the wnt signaling, beta-catenin, was upregulated in 42.9% of cases and transferred to the nucleus in 28.6% of metastasis cases. Our findings suggest that genetic changes of the tumor suppressor gene APC, a component of the wnt pathway, represent a part of the brain metastasis genetic profile.
authors: Laboratory of Neurooncology, Croatian Institute for Brain Research, School of Medicine, University of Zagreb, Šalata 12, 10000 Zagreb, Croatia. nina@mef.hr
authors: Nives
authors: N
authors: Pećina-Šlaus
authors: Tamara
authors: T
authors: Nikuševa Martić
authors: Martina
authors: M
authors: Zeljko
authors: Sandra
authors: S
authors: Bulat
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D054458:Amplified Fragment Length Polymorphism Analysis; D001483:Base Sequence / Q000235:genetics; D001932:Brain Neoplasms / Q000235:genetics; D019003:Deoxyribonuclease HpaII / Q000378:metabolism; D015252:Deoxyribonucleases, Type II Site-Specific; D005260:Female; D017491:Genes, APC / Q000502:physiology*; D006023:Glycoproteins / Q000235:genetics; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000235:genetics*; D017384:Sequence Deletion; D060449:Wnt Signaling Pathway / Q000235:genetics; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: D006023:Glycoproteins; D051176:beta Catenin; D019003:Deoxyribonuclease HpaII; D015252:Deoxyribonucleases, Type II Site-Specific; C040158:GTAC-specific type II deoxyribonucleases