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
K. Kumon et al., 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, JPN J CANC, 92(8), 2001, pp. 854-862
In a cytogenetic and comparative genomic hybridization (CGH) study of 38 he
patoblastomas, 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 o
f 4q in 4 (10.5%) and no DNA copy changes with normal karyotype or no mitot
ic 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 wi
th an augmented partial 2q region; the common region for DNA copy gain was
2q24. Two-color fluorescence in situ hybridization (FISH) analyses using pr
obes covering the centromere of chromosome 2 or HOXD13 (2q31) confirmed the
CGH findings, and showed that the common region for gain in 2q was centrom
eric 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 cha
nges other than 2q gain [74 +/- 13%] (P=0.0549). Multivariate analysis show
ed 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.