DNA sequence copy number increase at 8q: a potential new prognostic marker in high-grade osteosarcoma.
Histologic response to chemotherapy is currently the best prognostic parameter in high-grade osteosarcoma but it can be evaluated only after several weeks of chemotherapy. Thus a prognostic parameter known at the time of diagnosis would be of great clinical benefit. In the present study, we present the results of 31 primary high-grade osteosarcomas analyzed by comparative genomic hybridization (CGH). CGH allows for genome-wide screening of a tumor by detecting alterations in DNA sequence copy number. The most frequent aberrations were copy number increases at 1q21 in 58% of the tumors and at 8q (8q21.3-q22 in 52% and 8cen-q13 in 45%), followed by copy number increases at 14q24-qter (35%) and Xp11.2-p21 (35%). The most common losses were detected at 6q16 (32%) and 6q21-q22 (32%). Patients with a copy number increase at 8q21.3-q22 and/or at 8cen-q13 had a statistically significant poor distant disease-free survival (p = 0.003) and showed a trend toward short overall survival (p = 0.04). Patients with a copy number increase at 1q21 showed a trend toward short overall survival (p = 0.04). Thus, specific genetic aberrations detected at the time of the diagnosis could be used in prognostic evaluation of high-grade osteosarcoma.
Tarkkanen
M
M
Helsinki University Central Hospital, and Department of Medical Genetics, Haartman Institute, University of Helsinki, Finland. Maija.Tarkkanen@Helsinki.Fi
Elomaa
I
I
Blomqvist
C
C
Kivioja
A H
AH
Kellokumpu-Lehtinen
P
P
Böhling
T
T
Valle
J
J
Knuutila
S
S
D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D001859:Bone Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D002869:Chromosome Aberrations / Q000235:genetics*; D002872:Chromosome Deletion; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D005260:Female; D005784:Gene Amplification; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009693:Nucleic Acid Hybridization / Q000379:methods; D012516:Osteosarcoma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D011379:Prognosis
D005819:Genetic Markers