Frequent increase of DNA copy number in the 2q24 chromosomal region and its association with a poor clinical outcome in hepatoblastoma: cytogenetic and comparative genomic hybridization analysis.
In a cytogenetic and comparative genomic hybridization (CGH) study of 38 hepatoblastomas, we found gain of 1q in 17 tumors (44.7%), that of 2 / 2q in 14 (36.8%), that of 20 / 20q in 9 (23.7%) and that of 8 / 8q in 8 (21.0%), loss of 4q in 4 (10.5%) and no DNA copy changes with normal karyotype or no mitotic cells in 11 (28.9%). Eleven tumors with 2 / 2q gain detected by CGH had a total chromosome 2 gain, a partial 2q gain, or a total chromosome 2 gain with an augmented partial 2q region; the common region for DNA copy gain was 2q24. Two-color fluorescence in situ hybridization (FISH) analyses using probes covering the centromere of chromosome 2 or HOXD13 (2q31) confirmed the CGH findings, and showed that the common region for gain in 2q was centromeric to HOXD13. Event-free survival (EFS) +/- standard error (SE) at 5 years was lowest in patients with 2q gain [37 +/- 15%], highest in those with no DNA copy changes [82 +/- 12%], and intermediate in those with DNA copy changes other than 2q gain [74 +/- 13%] (P = 0.0549). Multivariate analysis showed that 2q gain was an independent factor predicting a poor outcome. These findings suggest the presence of a growth-promoting gene or an oncogene in the 2q24 chromosome band, and a tumor suppressor gene in terminal 4q, which have important roles in the development and progression of hepatoblastoma.
Kumon
K
K
Department of Cancer Chemotherapy, Saitama Cancer Center Hospital, Ina, Saitama 362-0806, Japan.
Kobayashi
H
H
Namiki
T
T
Tsunematsu
Y
Y
Miyauchi
J
J
Kikuta
A
A
Horikoshi
Y
Y
Komada
Y
Y
Hatae
Y
Y
Eguchi
H
H
Kaneko
Y
Y
D000970:Antineoplastic Agents / Q000627:therapeutic use; D002675:Child, Preschool; D002869:Chromosome Aberrations; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics*; D005260:Female; D018628:Gene Dosage; D016678:Genome; D018197:Hepatoblastoma / Q000235:genetics* / Q000401:mortality; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D007231:Infant, Newborn; D007564:Japan / Q000453:epidemiology; D007621:Karyotyping; D008113:Liver Neoplasms / Q000235:genetics* / Q000401:mortality; D008297:Male; D009693:Nucleic Acid Hybridization; D015996:Survival Rate
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm